RESUMO
The CD11/CD18 complex of leukocyte adhesion molecules has been shown to bind LPS on the surface of gram negative bacteria and LPS-coated erythrocytes (J. Exp. Med. 164:1876, 1986). LPS elicits several responses in leukocytes including secretion of TNF-alpha and IL-1 beta, and priming for enhanced release of oxygen radicals such as superoxide anion. To determine if expression of CD18 molecules is necessary for these effects of LPS, we have examined the responses of leukocytes from CD18-deficient patients. Three of the patients in this study are characterized for the first time here, and three were described elsewhere. Monocytes and macrophages from CD18-deficient patients synthesized normal amounts of IL-1 beta and TNF-alpha in response to LPS. Further, PMN and monocytes from CD18-deficient patients showed normal priming for enhanced release of superoxide anion in response to LPS. Although a small contribution of CD18 molecules to some responses cannot be ruled out by our data, we may conclude that CD18 molecules are not essential for cellular responses to LPS.
Assuntos
Antígenos CD/deficiência , Interleucina-1/biossíntese , Síndrome da Aderência Leucocítica Deficitária , Leucócitos Mononucleares/fisiologia , Lipopolissacarídeos/farmacologia , Neutrófilos/fisiologia , Superóxidos/metabolismo , Fator de Necrose Tumoral alfa/biossíntese , Actinas/metabolismo , Antígenos CD/análise , Antígenos de Diferenciação/deficiência , Antígenos de Diferenciação/fisiologia , Antígenos CD11 , Antígenos CD18 , Citometria de Fluxo , Humanos , Receptores de Adesão de Leucócito/fisiologiaRESUMO
Polymorphonuclear leukocytes (PMN) from three patients deficient in the CD18 family of receptors (LFA-1, CR3, and p150,95) exhibited an inability to bind erythrocytes coated with C3bi or bacterial LPS. These observations confirm that the CD18 family, and CR3 in particular, can bind the structurally dissimilar molecules C3bi and LPS. Further studies showed that LPS and C3bi bind to CR3 at distinct sites. mAb OKM10 against CR3 blocked binding of C3bi to PMN but did not block the binding of LPS. In contrast, mAb 904, directed against a different epitope on CR3, blocked binding of LPS to PMN but not binding of C3bi, thus suggesting that different regions of CR3 were involved in binding these two ligands. In addition, synthetic peptides based on the sequence in C3bi recognized by CR3 competitively blocked the binding of C3bi to CR3 but did not block the binding of LPS. Rather, occupation of the peptide binding site on CR3 by the synthetic peptides enhanced binding of LPS. These results indicate that CR3 has two distinct binding sites, one that recognizes ligands composed of protein and a second that recognizes LPS.
