Neutrophil adhesion to factor H

In this study, human complement factor H, a known regulatory protein of the Alternative Pathway of Complement, is shown to function as an adhesion ligand for human PMNs, but not for eosinophils. The adherence of PMNs to plastic wells coated with factor H depended on divalent metal ions and was augmented by CSa and TNFcc. PMN adhesion to factor H was found to be mediated by CD11a/CD18, and was specifically blocked by monoclonal antibodies against CD11a or CD18. The presence of surface bound factor H resulted in a 2 to 5-fold increase relative to control proteins (human serum albumin and C9) in the generation of HaOa by PMNs stimulated by C5a or TNFoc. PMNs resident on factor H also released a 1.5 to 2-fold greater amount of lactoferrin than cells on control proteins. A cooperation between glycosaminoglycan and factor H for PMN adherence was observed. When factor H at plasma concentrations was mixed with PMNs, cell adhesion to heparin or chondroitin A increased 1.4 to 3.8 fold. Also, significantly augmented adhesion of PMNs was measured when factor H, but not control proteins, was absorbed to wells which were first coated with heparin or chondroitin A. These studies identify factor H as an adhesion molecule for PMNs, and suggest that the interaction of factor H with glycosaminoglycans may serve to fix this protein in tissues.