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Different signaling pathways for CD18-mediated adhesion and Fc-mediated phagocytosis. Response of neutrophils to LPS.

1994; American Association of Immunologists; Volume: 153; Issue: 5 Linguagem: Inglês

10.4049/jimmunol.153.5.2137

1550-6606

P A Detmers, D Zhou, D E Powell,

Platelet Disorders and Treatments

Abstract The regulation of CD11b/CD18 adhesive and phagocytic functions on human polymorphonuclear leukocytes (PMN) in response to LPS was examined. Adhesion of PMN to surfaces coated with LPS had little or no effect on the cells, but pretreating the LPS-coated surfaces with either diluted serum or LPS-binding protein strongly enhanced their ability to bind C3bi-coated E (EC3bi), a ligand for CD11b/CD18. LPS-binding protein is known to enable responses of cells to LPS by facilitating binding of LPS to CD14. Consistent with this, we found that preformed complexes of LPS with soluble rCD14 stimulated binding of ligand by CD11b/CD18 in a concentration-dependent manner. Known agonists that stimulate CD11b/CD18 binding activity on PMN all cause simultaneous enhancement of Fc-mediated phagocytosis. However, LPS presented in complex with either serum proteins or CD14 failed to stimulate the ingestion of ElgG by PMN. The number of FcRs and their ability to bind ligand were not affected by treatment with LPS, nor were they compromised in their ability to respond to other agonists. These results suggest that LPS generates intracellular signals that alter the ability of CD11b/CD18 to bind ligand, but this alteration is not sufficient to promote phagocytosis of IgG-coated particle. This conclusion was confirmed by showing that PMN treated with LPS and serum produced a lipid with the properties of integrin-modulating factor 1: acetone extracts of these cells stimulated CD11b/CD18 adhesive capacity on PMN. However, the lipid did not enhance Fc-mediated phagocytosis. These studies suggest that CD14 affects CD11b/CD18 function by inducing the synthesis of a lipid such as IMF-1, and that this lipid affects only the binding activity, not the phagocytosis-promoting capacity of CD11b/CD18.