Review: group as receptors for bacteria and parasites

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Abbreviations: Gal = galactose; Glc = glucose; NeuAc lectins.4 Lectins are a class of of nonimmune = N-acetylneuraminic acid; GlcNAc = N-acetylglu- origin that can combine with sugars rapidly, selective- cosamine; GalNAc = N-acetylgalactosamine; FUC = ly, and, since binding is noncovalent, reversibly. Lectins fucose; Cer = ceramide. are not confined to plants but are widespread through- out nature, and frequently appear on surfaces of cells, An important phase in the initiation of diseases caused where they are strategically positioned to combine by bacterid and parasites is the adhesion of the infectious with complementary sugars on neighboring cells. agent to tissues of the mammalian host. Adhesion is Lectins are exquisitely specific; they can distinguish mediated by specificligand- interactions. Host between different monosaccharides and specifically cell receptors include a number of structures carrying bind to oligosaccharides, detecting subtle differences blood group antigens. A selection of such receptors and in complex carbohydrate structures. the attaching microorganisms, mostly bacteria, are listed Bacterial attachment to epithelial cells and to RBCs in Table 1 and will be reviewed in this article. results from the interaction of host cell receptors with bacterial surface structures known as fimbriae or pili.5 Table 1. Receptors for bacteria and parasites These submicroscopic hair-like appendages are 5 to 10 Receptors Bacteria and parasites nanometers in diameter and several hundreds of Ii Mycoplasmapneumuniae nanometers long. They protrude from the surface of P1, P, andPk P-fimbriated Escherichia coli the bacteria and serve as bacterial-binding factors by AnWj Haemophilus influenzae producing lectin-like adhesins or hemagglutinins. Dra 075X-adhesin of Escherichia coli Fimbriae-bearing surface lectins are not restricted to E. FY Plasmodium vivax Plasmodium knowlest coli. A particular strain of bacteria may produce more A, R, C, D PIasmodium falciparum than one fimbrial type at the same time; each fimbrial N-acetylneuraminic acid type is usually on a different bacterium. Fimbriae may be characterized by the hemagglutinin produced. The The adhesive capacity of bacteria was first described common type 1 fimbriae bind the sugar mannose and by Duguid et al. These workers demonstrated that are therefore termed “mannose sensitive,” since many strains of Escherichia (E.) coli, an organism caus- hemagglutination is inhibited by mannose.* Various ing intestinal and extraintestinal infections, adhered to “mannose resistant” adhesins have been identified on cells from the epithelial lining of tissues and to red E. coli strains: P fimbriae of pyelonephritogenic E. coli blood cells (RBCs). The presence of the bacteria caused bind the disaccharide Gala(1-4)Gal, which is found in red cell clumping, commonly referred to as hemagglu- human blood group P glycosphingolipids (thus the tination. Hemagglutination is specific and, depending term P fimbriae) and antigens of the collec- on the bacterial strain, can be inhibited by specific sug- tion.6.7 Other mannose-resistant fimbriae make up a ars, including the monosaccharidemannose. heterogeneous group and are termed X-adhesins: these Sugars play a vital role in cell-to-cellrecognition and include S fimbriae, which recognize sialylgalactosides cell-to-celladhesion, and are found on (NeuAca[2-31Galß[1-3]GalNAc)of glycophorinA and the surface of most cells. Receptor recognition and may be important in the pathogenesis of neonatal interaction is mediated by carbohydrate2,3 and meningitis.* E. coli-075X strains produce an X-adhesin

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that is referred to as the Dr hemagglutinin, since ognized by the cold autoantibodies anti-Gd and anti-FI Dr(a+) RBCs but not Dr(a-) RBCs are agglutinated by (Table 2); anti-I is an autoantibody directed against the this adhesin.8 backbone structure of the receptor.7,10 König et al.10 found that 53 percent of 192 patients Mycoplasma pneumoniae and Ii with recent M. pneumoniae infection had co-existing Mycoplasma (M.) pneumoniae infection has long anti-I and anti-FI/Gd in their serum. These patients had been associated with an increase in titer and thermal responded to the entire receptor structure, although in range of autoanti-I. The antibody was thought to be pro- the same study 22 percent of the sera contained only duced in response to an M. pneumoniae and to anti-I. be cross-reactive with an RBC antigen, presumably I related. Loomes et al.9 suggested that these autoanti- Haemophilus inauenzae and AnWj bodies occurred as a result of the interaction of I antigen Haemophilus (H.) influenzae is found in the throat with M. pneumoniae and of the presentation of this of most healthy people, but can cause respiratory tract altered "self" antigen to the immune system. infections. This organism is a major cause of bacterial The attachment of radiolabeled RBCs to M. pneumo- meningitis in young children. Fimbriated strains of H. niae cultures was inhibited by oligosaccharides, glyco- influenzae will agglutinate RBCs, and the fimbriae pro- proteins, and glycolipids containing chains of the mote bacterial adherence to nasopharyngeal cells. branched I or linear i antigen structures, provided that In 1986, van Alphen and his colleagues" showed NeuAc (sialic acid) was present in a terminal position. that the high-incidence antigen AnWj (called Anton at Linear oligosaccharide chains containing repeating N- that time) is the RBC receptor for H. influenzae. This acetyllactosamine residues (GAPß[ 1-41 GlcNAc) give rise work was extended in later publications. AnWj is pre- to i antigen; I antigen results from repeated branching sent on RBCs of most people, but is lacking or marked- of this chain by addition of more Galß(1-4)GlcNAc units ly suppressed on RBCs of the Lu(a-b-) (Table 2). It was concluded that the structure caused by In(Lu), a rare dominant independent of NeuAca(2-3)Galß(1-4)GlcNAc is recognized by, and the Lu locus. AnWj is also absent from cord RBCs and acts as a receptor for, M pneumoniae. The receptor is RBCs from those rare people with anti-AnWj in their made immunogenic by the binding of the bacteria. The serum or with the inherited AnWj- phenotype.12 complete structures that were identified as receptors for Although AnWj antigen is the structure on RBCs M. pneumoniae are identical to the RBC antigens rec- bound by H. influenzae, the establishment of infection

3) Gd antigen Galß(1-4)GlcNAc/Glc 6)

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requires binding to epithelial cells of the respiratory disposes females to UTIs. The presence of differentfim- tract. Initially, van Alphen et al.11 concluded that the brial types is correlated with different types of UTIs: P epithelial cell receptor and the RBC receptor for H. and S fimbriae are correlated with pyelonephritis, Dr influenzae fimbriae are expressed independently. 13 hemagglutinins with cystitis, and type 1 fimbriae (the This conclusion was based on the observation that H. common type) with lower UTIs.18 influenzae adhered to buccal epithelial cells, but not to RBCs from healthy neonates, nor to RBCs from an P-fimbriated E. coli AnWj- person with anti-AnWj. Recent studies showed P-fimbriated E. coli were so named when it was that the failure of H influenzae to bind to these RBCs found that they would hemagglutinate all RBCs except was caused by suppression of the red cell receptor, tem- those of the p phenotype, a null phenotype lacking all porarily in the case of cord cells and transiently in P system antigens,6 and antigens of the globoside col- AnWj- persons having and-AnWj in their serum, rather lection. P fimbriae bind to host cell surfaces through than by genetic events. The finding of an Arab-Israeli recognition of the disaccharide Gala(1-4)Gal present in family with three AnWj- siblings demonstrated that the the oligosaccharides attached to membrane glycolipids AnWj- phenotype may be an inherited characteristic.14 of the host cell. Testing of AnWj- and AnWj+ members of this family Serologically, we recognize these Gala(1-4)Gal- showed concomitant inheritance of the epithelial and containing glycosphingolipids as P1, antigen, P antigen RBC receptors, proving joint inheritance of the genetic (globoside), and Pk antigen (Table 3). On P1 and Pk gly- information for both receptors.15 However, despite this cosphingolipids, Gala(1-4)Gal is in a terminal position, common genetic background, the two receptors must while in globoside (P antigen), Gala(1-4)Gal is in an be different, since anti-AnWj inhibited only hemaggluti- internal position. E coli can combine with glycosphin- nation of AnWj+ RBCs and not adherence to buccal golipids that have the disaccharide in a terminal position epithelium. Evidence shows that the receptor is likely or when the disaccharide is part of the inner structure to be sugar, and lipids are unlikely to be involved. of the molecule. Therefore, E coli have a choice of P, P1, AnWj, and thus the receptor for H. influenzae, may and Pkantigens as attachment sites. Indeed, E. coli may be associated with the erythrocyte CD44 . prefer the internal version of the disaccharide, because Parsons et al. 16 described a child with a novel form of of the greater conformational stability of the receptor in dyserythropoietic anemia whose RBCs were AnWj-; this position. A subtype of P fimbriae, encoded by the these RBCs had a marked deficiency of the erythrocyte pap-2 gene cluster, uses LKE antigen (stage-specific membrane CD44 glycoprotein. embryonic antigen 4, SSEA-4) as its receptor.18 This complex binding site, an internal portion of the E. coli and urinary tract infections molecule, is composed of Galp(1-3)GalNAcß(1-3) The establishment of ascending urinary tract infec- Gala(1-4)Gal. tions (UTIs) requires bacterial adhesion to tissue sur- These Gala( 1-4)Gal-containing glycosphingolipids faces of the urinary tract. Attachment of infecting strains are thought to project from the uroepithelial surface, to specific receptors may be mediated by fimbrial (and permitting attached E. coli to progress across the surface nonfimbrial) adhesins. E. coli is the causative agent of of the bladder epithelium in a ladder-like fashion against most UTIs. Organisms from the bowel may colonize the the downward flow of urine, ultimately gaining access periurethral area, and from there establish colonization to the renal pelvis, where pyelonephritis may become of the urinary tract through the urethra, bladder, and established. Since RBCs of the p phenotype are not ." The short urethra of the female permits the agglutinated by pyclonephritogenic E. coli and the organisms to have easy access to the bladder and pre- bacteria have impaired adhesion to uroepithelial cells

Table 3. Structuresof p,, Pk, p, and LKE antigens

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from p individuals, it is inferred that individuals of the p brane by a glycosylphosphatidylinositol anchor (GPI- phenotype have enhanced resistance to UTI and linked).25,26 Lack of GPI-linked complement regulato- pyelonephritis. It was suggested that there is a greater ry proteins, including DAF, is responsible for the incidence of UTI and recurrent pyelonephritis among seen in patients with the most severe form P1+ women, rather than among P1- women.19 of the acquired disease paroxysmal nocturnal hema- However, this theory was disputed by a study that asso- globinuria (PNH III). Since PNH IIIRBCs lack DAF, they ciated Lewis and with recurrent UTI in lack all Cromer antigens, including Dra, and thus are not women. In a study of 49 white women with recurrent agglutinated by the 075X-adhesin of E. coli. UTI, Sheinfeld et al.20found a significantly higher fre- The structure of DAF has been determined by N-ter- quency of Le(a+b-) and Le(&-) nonsecretors.20 They minal sequencing and cloning of DAF cDNA suggest that there is decreased availability of putative (see references 25 or 26 for diagrams). As with other receptors for E coli in women with the Le(a-b+) secre- GPI-linked proteins, DAF has multiple homologous tor phenotype, since the uroepithelium of persons with regions, or domains, termed short consensus repeat the secretor phenotype is rich in ABH and Leb determi- regions (SCR). DAF is composed of four such domains. nants; these determinants are thought to shield the A single-point mutation, a C-to-T change in codon 165, receptors for E. coli. Similarly, Lomberg et al.21 found results in an change of to in that the ability of bacteria to bind to epithelial cells is the third SCR, and accounts for the difference between increased in nonsecretors of ABH when compared with the Dr(a+) and Dr(a-) . This serine-to- secretors. Lurie et al.22 reported that the ABO, Lewis, or leucine change may reduce the possible O- P blood group phenotypes are not associated with and amount of NeuAc in the Dra region of the . recurrent pelvic inflammatory disease. Reduced O-glycosylation may prevent buiding of E. coli Both the globoside and the P1 antigen structure are in Dr(a-) people.25Exactly how, and whether, the ser- widely distributed in nature. Sources of soluble P1 sub- ine-to-leucine mutation site is involved in receptor func- stance include hydatid cyst fluid, pigeon egg white, and tion is still uncertain, particularly since Nowicki et al.8 dove egg white. Avian P1 substance was recently report- specifically inhibited the binding of Dr hemagglutinin to ed to inhibit hemagglutination by P-fimbriated E. RBCs by chloramphenicol, and by a modified tyrosine molecule with a structure similar to chloramphenicol. Dr hemagglutinin Another strain of uropathogenic E. coli recognizes as Dr receptor sites its receptor Dra, a high-incidence antigen of the Cromer The primary function of DAF is down-regulating com- blood group system. Dra and the other Cromer antigens plement activation by preventing the formation of C3 are carried on the complement regulatory protein, and C5 convertases and dissociating preformed conver- decay-acceleratingfactor (DAF). Cromer antigens are tases. Broad tissue distribution of DAF and, therefore, related serologically by several common characteristics. Dra on RBCs, leukocytes, , and epithelial cells is They are mostly antigens of very high incidence that are to be expected. Host susceptibility for infectious dis- lacking from RBCs of the rare null “Inab”phenotype. eases is influenced by the density and accessibility of The Dr(a-) phenotype has greatly reduced expression receptors. Investigation of density and distribution of of all other Cromer antigens. Only three apparently receptors for Dr-positive E. coli on various tissue sec- unrelated families with the Dr(a-) phenotype are tions using indirect immunofluorescence revealed known; all are Israeli Jews who originated in the intense staining in a section through the colonic glands Bukharan region of Uzbekistan (for reviews of Cromer and in a section through the ureter; the transitional and DAF, see references 24 and 25). epithelial cells in the ureter were heavily stained. The Nowicki and his colleaguess found that cells of the Bowman’s capsule of the kidneys and renal tubular base- Inab phenotype were not agglutinated by the 075X- ment membranes were also shown to be rich in Dr adhesin of E. coli. When cells lacking individual Cromer receptors.27 This mass of Dr receptors in the colon system antigens were tested, only Dr(a-) cells were not permits colonization by Dr-positive E. coli and subse- hemagglutinated. The Dra-carrying glycoprotein (DAF) quent colonization of the periurethral area. To develop belongs to a class of entirely extracellular membrane ascending colonization and infection, an army of bacte- , which are anchored to the RBC mem- ria may use the potential binding sites on the transition-

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al epithelium lining the bladder and ureters, and even- that requires the presence of Duffy antigens.33 The tually reach the kidneys. invasion site is probably on the same molecule as Fya Receptors for P fmbriae of pyelonephritogenic E. coli and Fyb and/or Fy6. The invasion of - or neu- are mainly in the kidney glomeruliand the lumens of the raminidase-treated Fy(a-b-) RBCs by I! knowlesi may proximal and distal kidney tubules (the upper urinary suggest a third invasion site, revealed by the removal of tract),17 so it is not surprising that these bacteria are com- NeuAC.34 monly associated with upper UTI, whereas Dr-hemag- A monoclonalantibody produced by Nichols et glutinating E. coli are found in lower UTI or cystitis. designated anti-Fy6, binds a unique determinant on the Duffy protein, which is found on all RBCs except Malaria and Duffy Fy(a-b-) cells. The presence of this epitope on various Human malaria is caused primarily by three species human and nonhuman primate RBCs correlates with of Plasmodium:Plasmodium (P.) vivax, I?falciparum, invasion of I! vivax, suggesting that Fy6 may constitute and I! malariae. P. vivax, is the most common and wide- a binding site on the RBC. Duffy antigens are carried on ly distributed species, while I! falciparum is the most a glycoprotein with an apparent molecular weight of virulent.28 I? knowlesi, which causes rapid death in 35,000-43,000 kDa.36 A protein with biochemical Rhesus monkeys, causes only relatively mild and tem- characteristics similar to the Duffy glycoprotein is the porary infection in man. An essential stage of the com- erythrocyte chemokine receptor, a receptor for a num- plex life cycle of malarial parasites is the invasion of host ber of chemokines including interleukin-8 (IL-8) and RBCs by merozoites. In the RBC, the merozoites under- melanoma growth stimulatory activity (MGSA). Horuk go growth and nuclear division before developing into and colleagues37observed that a high percentage of either an asexual parasite or a sexual gametocyte. This African Americans had RBCs that did not bind IL-8 and invasion involves interaction between receptors on the that these RBCs were Fy(a-b-). There was absolute parasite and ligands, or binding molecules, on the sur- association of IL-8 binding and the Duffy positive phe- face of the host cell. Details and references for the work notype, indicating that the erythrocyte clieinokine summarized below may be found in two excellent receptor is the Duffy blood group antigen or that they review articles.28,29 are closely liked. The same study demonstrated that In 1955 two interesting papers on this subject were IL-8 and MGSA block the binding of P. knowlesi to RBCs published. One stated that a high percentage of expressing Duffy antigens. Anti-Fy6, which inhibits the American and African blacks were resistant to blood- binding of I! knowlesi to Duffy positive RBCs,35 inhib- induced infections with P. vivax.30 The other paper stat- ited the binding of IL-8 in a dose-dependent manner. ed that the majority of American and African blacks Binding to the erythrocyte chemokine receptor of were Fy(a-b-).31 Twenty years later it was shown that three other chemokines (MGSA, MCP-1, and RANTES) red cells lacking Fya and Fyb antigens are resistant to was also inhibited by anti-Fy6. Thus, since anti-Fy6 was invasion by I? vivax, in vivo and by the Simian malarial previously found to block invasion of RBCs by P. vivax, parasite I! knowlesi in by inference the erythrocyte chemokine receptor is a Cytochalasin B-treated merozoites are able to attach receptor for P. vivax. Molecular cloning may determine to red cells but cannot invade them.33 Electron micro- whether or not the Duffy glycoprotein and the graph studies of these handicapped merozoites showed chemokine receptor are the same protein. The recep- their attachment to Fy(a-b-) RBCs as well as to Duffy- tor blocking experiments described by Horuk et positive cells, but the nature of the attachment to suggest that receptor blocking therapy, using drugs Fy(a-b-) RBCs was different. With Duffy-positive RBCs, modeled on the structure of IL-8 and MGSA, could be the parasite forms a junction, referred to as a moving useful therapeutically. junction. This junction is not formed with Fy(a-b-) RBCs. Instead, attachment is characterized by fine fib- N-AcetylneuraminicAcid and Malaria rillar material extending between the merozoite and In contrast to P. vivax, P.falciparum infects people the red cell membrane. These observations are consis- equally, regardless of Duffy type, indicating that P. falci- tent with the need for two receptors for invasion to parum uses a different receptor for invasion.38 N-acetyl- occur: one for attachment of merozoites regardless or neuraminic acid (NeuAc), or sialic acid, is an important independent of Duffy type, and the other for invasion receptor for invasion by this parasite. Most of the NeuAc

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on the RBC is found on (GPA) and gly- sidered to be a nonspecific consequence of an alteration cophorin B (GPB), the carrying the in red cell deformability resulting from the binding of an MN and the Ss and U antigens, respectively NeuAc is antibody close to the cell membrane. also found, though to a lesser extent, on glycophorin C Much is known about the invasion of the RBC by (GPC) and D (GPD), the molecules carrying the antigens malarial parasites, but even more questions remain of the Gerbich system. unanswered about this multistep process. The precise Miller et al.38 observed that GPA-deficient RBCs, that conformation and linkage of NeuAc-dependent recep- is, cells lacking the MN (En[a-] tors fort?falciparum is awaiting definition. cells), are more resistant to invasion than normal RBCs. Furthermore, they demonstrated that En(a+) cells sen- Conclusion sitized with anti-En" had reduced invasion by t? falci- This article has attempted to highlight the involve- parum. Invasion of normal cells was reduced when ment of blood group antigens and some of the fascinat- NeuAc was removed by treatment with ing ways microorganisms gain access to the human or when soluble GPA was added to the parasite-red body to establish infection. Other organisms, not cell mixture. Similar findings were reported by Pasvol described here, are also believed to use blood group et al.39 antigens as receptors. G fimbriae of the IH1 1165 strain S-s-U- cells lack GPB; such RBCs were less suscepti- of E. coli produce a hemagglutinin with specificity for ble to invasion than cells with Ss antigens, but were terminal NeuAc residues on GPA. The same strain pro- substantially less resistant than En(a-) RBCs. Some resis- duces an M agglutinin with specificity for M antigen; this tance to invasion was observed with GPC- and GPD-defi- can be inhibited by L-serine.41 Some parasites can cient RBCs of the rare Gerbich null phenotype, the escape the immune response of the host by adsorbing Leach phenotype. However, this resistance could be due structures carrying blood group antigens; e.g., to the abnormal RBC morphology rather than to lack of Schistosoma mansoni can adsorb the DAF molecule NeuAc, since RBCs lacking GPC and GPD are ellipto- from the host, thus resisting destruction by the alternate cytic and more rigid than normal RBCs. Rigidity may pathway of complement.42 Trypanosoma cruzi pro- interfere with either binding or entry of the parasite. duces a protein homologous to human DAF at the pro- The finding that neuraminidase treatment of normal tein and DNA levels.43 RBCs reduced invasion by P. falciparum by 50 percent Information on bacterial receptors accumulated over alerted Miller et al.38 to the importance of NeuAc clus- time may have relevance in the treatment of infections. tered on O-linked oligosaccharides or O-glycans, found Since urinary tract infections may be caused by one or on glycophorin molecules. Tn RBCs, which lack NeuAc more strains of bacteria, treatment often varies accord- and Gal from these @glycans, are virtually refractory to ing to strain. Agglutination tests using RBCs, or a recep- invasion by some strains of P. falciparum Cad pheno- tor carrier molecule such as latex beads coated with type RBCs have an additional GalNAc residue attached relevant sugar receptors, may provide a quick and sim- to most O-glycans. This additional residue may prevent ple way to distinguish the different bacterial strains in a access of the parasite to its NeuAc receptor, and may be sample of urine from a patient. the cause of the reduced rate of invasion of Cad pheno- Sugars, glycolipids,or glycoproteins that inhibit the type RBCs. binding of bacteria to epithelial cells in vitro significantly Confirmation that only some strains of P. falciparum reduce the rate of urinary tract infection in experimen- are dependent on NeuAc for invasion came from tests tal animals.* So far, this work has not been extended to with RBCs deficient in GPA and GPB, that is, MkMk humans, in part because of the possibility that such sub- RBCs. For other strains, although invasion is somewhat stances may lead to increased infection. Globoside and reduced in the absence of NeuAc, the main receptor for other glycolipids have the ability to insert into lipid invasion is through a NeuAc-independent, trypsin-sen- membranes, thus increasing the number of bacterial sitive receptor. binding sites. This ability was illustrated by the finding Contrary to earlier reports, Wrb is no longer consid- that p erythrocytes were agglutinated by P-fimbriated ered to be a receptor for P.falciparum merozoites, since bacteria after, but not before, incubation with globo- Wr(a+b-) RBCs are invaded normally.40The effect of side.23 Until this process is understood, sugars are anti-Wrb in inhibiting merozoite invasion is now con- unlikely to replace antibiotics as treatment.

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Serologists continue to wonder about the functions 6. KälleniusG, MollbyR, Svenson SB, et al. The P antigen as recep- of RBC antigens; however, it seems unlikely that they tor for the hemagglutinin of pyelonephritic Escherichia coli. FEMS Microbiol Lett 1980;7:297-302. evolved to be specific receptors for infectious organ- 7. Moulds JM, Woods LL, eds. Blood groups: P, I, Sda and Pr. isms. We should perhaps marvel at the adaptability of Arlington, VA: American Association of Blood Banks, 1991. microorganisms, which has allowed them to take advan- 8. Nowicki B, Moulds J, Hull R, Hull S. A hemagglutinin of tage of existing host structures. uropathogenic Escherichia coli recognizes the Dr blood group antigen. Infect Immun 1988;56:1057-60. Addendum 9. Loomes LM, Uemura K-I, Childs RA,et al. Erythrocyte receptors for Mycoplasma pneumoniae are sialylated oligosaccharides of Since this article was written, several important Ii antigen type. Nature 1984;307:560-3. papers have been published that are pertinent to this 10. König AL,Kreft H, Hengge U, Braun RW, RoelckeD. Coexisting review. Leb (Lewisb) antigen was shown to mediate the anti-I and anti-FI/Gd cold agglutinins in infections by Mycoplasma pneumoniae. Vox Sang 19888;55:176-80. attachment to human gastric mucosa of Helicobacter 11. van Alphen L, Poole J, Overbeeke M. The Anton blood group pylori (H.pylon), a causative agent in chronic active gas- antigen is the erythrocyte receptor for Haemophilus influen- tritis, gastric and duodenal ulcers, and gastric zae. FEMS MicrobiolLett 198637:69-71 12. Daniels G. The Lutheran blood group system: monoclonal anti- adenocarcinoma.44 Gastric tissue lacking Leb did not bodies, biochemistry and the effect of In(Lu). In: Pierce SR, bind H. pylori. Bacterial binding could be inhibited by Macpherson CR, eds. Blood group systems: Duffy, Kidd, and soluble glycoproteins presenting the Leb antigen, or by Lutheran. Arlington, VA: American Association of Blood Banks, antibodies to the Leb antigen. H antigen, on a Type 1 car- 1988:119-47. 13. van Alphen L, PooleJ, Geelen L, Zanen HC. The erythrocyte and rier molecule, reduced binding of H. pylori to epithelial cell receptors for Haemophilus influenzae are gastric mucosa. expressed independently. Infect Immun 1987;55:2353-8. The only known pathogenic human parvovirus, B19, 14. PooleJ, Levene C,Bennett M, SelaR, van Alphen L, Spruell PJ. A family showing inheritance of the Anton blood group antigen causes fifth disease (erythema infectiosum), a mild AnWj and independence of AnWj from Lutheran Transfusion childhood illness. More seriously, the organism can Medicine 1991;1:245-51. cause transient aplastic crisis in patients with underly- 15. van Alphen L, Levene C, Geelen-van den Broek L, Poole J, ing hemolysis, and chronic anemia in immunocompro- Bennett M, Dankert J. Combined inheritance of epithelial and erythrocyte receptors for Haemophilus inflnuenzae. Infect missed patients. Parvovirus B19 replicates only in Immim 1990;58:3807-9. erythroid progenitor cells. It was reported by Brown et 16. Parsons SF, Jones J, Poole J, Anstee DJ, Illum N, Wickrama- aI.45 that the P antigen (globoside) was the major recep- singhe SN. An In(a-b-) individual whose red cells are deficient in CD44 glycoprotein also lacks the high incidence antigen tor for the B19 virus on erythroid target cells. AnWj. 1992;2:65. Monoclonal anti-P antibodies were used to prevent viral 17. Nowicki B, Holthöfer H, Saraneva T, Rhen M, Väisinän-KhenV, binding. B19 infection could be blocked by excess glo- Korhonen T. Location of adhesion sites for P-fimbriatedand for boside or by globoside-specific monoclonal antibody. 075X-positive Escherichia coli in the human kidney. Microbial Pathogenesis 1986;1:169-80. People with the p phenotype who have RBCs lacking P 18. KarrJF, Nowicki BJ, Truong LD, Hull RA, Moulds JJ, Hull SI. antigen were found to be naturally resistant to infection pup-2 encodedfimbriae adhere to the P blood grouprelated gly- with parvovirus B19, and the bone marrow from cosphingolipid stage-specificembryonic antigen 4 in the human kidney. Infect Immun 1990;58:4055-62. donors with the p phenotype could not be infected 19. LombergH, Hansen LA,Jacobsson B, et al. Correlation ofP blood in vitro.46 group, vesicoureteral reflux, and bacterid attachment in patients with recurrent pyelonephritis. N EnglJ Med 1983;308:1189-92. References 20. Sheinfeld J, SchaefferAJ, Cordon-Cardo C, Rogatko A, Fair WR. 1. DuguidJP, Smith W, Dempster G,Edmunds PN. NonflagellarN- Association of the Lewis blood-groupphenotype with recurrent amentous appendages ("fimbriae") and haemagglutinating activ- urinary tract infections in women. N Engl J Med 1989; ity in Bucterium coli. J Pathol Bacteriol 1955;70:335-48. 320:773-7. 2. Kuijpers TW. Terminal glycosyltransferase activity: a selective 21. Lomberg H, Cedergren B, Leffler H, et al. Influence of blood role in cell adhesion (review article). Blood 1993;81(4): groups on the availability of receptors for attachment of 873-82. uropathogenicEscherichia coli. Infect Immnn 1986;51:919-26. 3. Sharon N, Lis H. Carbohydrates in cell recognition. Scientific 22. Lurie S, Sigler E, Fenakel K. The ABO, Lewis, or P blood group American 1993;268:82-9. phenotypes are not associated with recurrent pelvic inflamma- 4. Sharon N. Lis H. Lectins as cell recognition molecules. Science tory disease. Gynecol Obstet Invest 1901;31:158-60. 1989;246:1227-34. 23. Johnson JR, Swanson JL, Neill MA. Avian P1 antigens inhibit 5. Knutton S. Lloyd DR. David CA. Candy A. McNeish AS. agglutination mediated by P fimbriae of uropathogenic Ultrastructural study' of adhesion of enterotoxigenic Escherichia coli. Infect Immun 1992;60:578-83. Escherichia coli to erythrocytesand human intestinal epithelial 24. 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Attention SBB Students. You are eligible for a free one-year subscription to Immunohematology.Ask your education supervisor to submit the names of stu- dents, complete addresses for each one, and the inclu- sive dates of the training period to Mary H. McGinniss, Managing Editor, Immunohematology, National Reference Laboratory for Blood Group Serology, American Red Cross, 15601 Crabbs Branch Way, Rockville, MD 20855-2736.

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