ABSTRACTS 1375

COMPLEMENT (BF, C2, C4) AND HLA MARKERS IN THE NORMAL FRENCH BASQUES. l G. Haupt- mannl, A, DeMouzon2, E. Ohayon2, J. Goetzl, M. Abbal2, J. Constans3, and J.Ducos2. ‘Centre de Transfusion Sanauine. Strasboura. France: *Unitd INSERM 100. and %entre d’l&motvooloaie du CNRS, Toulouse,?rande. -’

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The Basques are thought to be the last representatives of a primitive European population and have remained rather isolated until recently. They live in the western part of the Pyrdndes mountains and are very endogamous. They are characterized by two HLA haplotypes: Aw19.2(Aw30),Cw5,Bl&DR3 and Al,C-,B17,DR7 with high frequencies and strong linkage disequilibrium. A study of the HLA-associated complement markers BF, C2 and C4 showed: -a high frequency of the BF’Fl allele (.1393), a decrease of BF*S(.5497), and a slight increase of BF’F (.2960) as compared with the other European Caucasian populations. -the absence of electrophoretic variants of C2 other than C2*C. -a high frequency of the C4A*6§ (.105), C4B’QO (.227) genes and of the C4A*3 B’QO (.203) and C4A*6,B*l (.105) haplotypes as compared with the frequencies reported in a North American cauca- Sian population by Raum et al. (IMMUNOLOGY 80, Progress in Immunology IV, p.1247, Academic Press, 1980). -highly significant allelic associations between HLAB’17 and C4A.6 (lOO%§$) HLADR*7 and C4A.6 (82%), HLAB*18 and C4B*QO (85%), HLADR*S and C4B’QO(54%), BF*Fl and C4B”QO(lOO%).

The following two frequent haplotypes with strong linkage disequilibrium could be defined in this population: HLAA’19.2 (A*w30), HLAC’w5, HLAB’18, BF*Fl, C2*C, C4A’3, C4B*QO, HLADR*3, and HLAA*l, HLAC*-, HLAB’17, BF*S, C2*C, C4A*6, C4B*l, HLADR’7. In addition, an association of the genes HLAB*wSO, BF*SO.7, C2*C, C4A’2, C4B*l was observed in three unrelated individuals. 5 Hemolytically inactive variant, §§ Relative delta values. (Supported by INSERM grants CRL 78 7 091 1 and CRL 79 4 106 1)

COMPLEMENT MEDIATED EOSINOPHIL HISTAMINASE RELEASE. J.J. Herman’ and R. Schneider- man. Children’s Memorial Hospital, Northwestern University Medical School, Chicago, Illinois.

Complement (C3b) dependent histaminase release has been demonstrated for human polymor- phonuclear leukocytes (PMN), while eosinophil (EOS) histaminase release occurred independently in response to particle bound C3b. Therefore, experiments were done to further characterize the EOS response to fluid phase complement components.

Granulocytes demonstrated a response in histaminase release to zymosan treated serum (ZTS) (11.5 2 0.9%) and to zymosan treated C5 deficient serum (C5D) (18.2 rc_ 1.7%) as compared to control un- treated normal serum or C5D serum. When the cells were preincubated with Cytochalasin B (5 mcglml), the response in histaminase release was blocked comletely while beta-glucuronidase release was enhanced. When metrizamide graident (16-30%) purified EOS (190%) were incubated with ZTS, the histaminase release was 41 f 4.7%, and zymosan treated C5D induced 37.5+4.2% histaminase release. This histaminase release was blocked when the EOS were pretreated with Cytochalasin B; essentially no EOS histaminase release was demonstrated with zymosan treated C2 or C3 deficient serum, but histaminase release was increased in response to cobra venom factor activation of the alternate pathway in C3 deficient serum. Arylsulfatase release from EOS was dependent on particle bound C3b but was not demonstrated in zymosan treated C5D or upon activation of the alternate pathway.

Thus, histaminase release from the eosinophil appears to be dependent on activation of the atler- nate complement pathway.

HOST MODIFICATION OF SINDBIS VIRUS SIALIC ACID ALTERS ALTERNATIVE COMPLEMENT PATHWAY ACTIVATION IN VlTRO AND PATHOGENESIS OF INFECTION IN VIVO. Robert L. Hirsch l , Diane E. Griffin, and Jerry A. Winkelstein. Howard Hughes Medical Inst., Johns Hopkins Univ. Sch. Med., Baltimore, MD.

Previous studies have shown that Sindbis virus (SV) infections are more severe in complement (C)-depleted mice, primarily due to defective clearance of virus from their bloodstream. Furthermore, SV wash shown to be capable of activating the alternative pathway (ACP) in the absence of detectable antiviral immunoglobin. The present experiments were performed to determine if the sialic acid (NANA) content of SV regulates its ability to activate the ACP. Purified SV grown in baby hamster kidney (BHK-SV) and in mosquito (MOSQ-SV) cells yielded virus with 10.4 and < 1.0 nmoles NANAlmg viral protein, respectively. SV deficient in NANA (1.2 nmoles NANA/mg) was also produced by treating BHK-SV with neuraminidase (NANAse-SV). When MOSQ-SV or NANAse-SV was incubated in C4DGPS or CPDHS, each consumed significantly more C3 than did BHK-SV. Studies in mice showed that the MOSQ-SV was cleared much more rapidly than BHK-SV after i.v. injection. C3 depletion eliminated the differences in clearance rates, demonstrating that sialic acid influenced C-dependent clearance of virus.

The sialic acid content of SV is determined by the host in which it is propgated. Thus, it is possible that different hosts will modify SV sialic acid content to varying degrees and thereby influence the ability of the virus to activate the ACP and participate in host defense. When 74 outbred Swiss mice were injected subcutaneously with SV, a significant positive linear correlation (r = .374, P< .005) was obtained between the level of viremia and host erythrocyte sialic acid. These studies suggest that the amount of sialic acid acquired by the virus in an individual host will influence the ability of the ACP to participate in host defense against infection. (Supported in part by USPHS Grant NS15749 and A111637)