HUMAN MONOCYTE CHEMOTAXIS TO COMPLEMENT-DERIVED CHEMOTAXINS IS ENHANCED BY GC-GLOBULIN

Gc-globulin has been found in bronchoalveolar lavage fluid in patients with chronic obstructive pulmonary disease (COPD) and adult respirato ry distress syndrome (ARDS) and has been shown to enhance neutrophil c hemotaxis to CS-derived peptides in vitro. We proposed that Gc-globuli n may enhance the inflammatory response in lungs by influencing monocy te chemotaxis to CS-derived peptides as, it does with neutrophils. Mon ocyte chemotaxis was measured in blind well chambers by a leading-fron t technique. Purified human Gc-globulin had no intrinsic chemotactic a ctivity for monocytes at concentrations ranging from 1 fM to 1 mu M. H owever, Gc-globulin, at concentrations as low as 10 pM, increased mono cyte chemotaxis over 10-fold in a concentration-dependent fashion when added to nonchemotactic doses of C5a (0.1 nM) and C5a des Arg (0.5 nM ). The chemotaxis-enhancing effect of Gc-globulin was specific for CS- derived peptides, as Gc-globulin did not enhance monocyte chemotaxis t o other chemoattractants such as leukotriene B-4 or formyl-Met-Leu-Phe . The enhancement of monocyte chemotaxis to CS-derived peptides by Gc- globulin was not a nonspecific effect of anionic proteins, as other se rum proteins of similar size and charge did not enhance monocyte chemo taxis to C5a des Arg. These results indicate that Gc-globulin enhances the monocyte response to CS-derived peptides and, together with previ ous work, indicates that its presence in the airways of patients with COPD and ARDS may up-regulate the monocyte inflammatory response in th e lungs.