Fibronectin fragment(s) are chemotactic for human peripheral blood monocytes.
Both plasma-derived and cell-derived fibronectin are deposited at sites of inflammation and wound healing and are associated with migrating cell populations including monocytes/macrophages. We found that fibronectin fragments generated by endogenous protease(s) are potent chemoattractants for human peripheral blood monocytes, whereas intact fibronectin has no activity. Fibronectin preparations produced by gelatin affinity chromatography in the absence of protease inhibitors contained 90 to 220 kd fragments and had potent chemotactic and chemokinetic activity for monocytes but no activity for human neutrophils or lymphocytes. The addition of phenylmethylsulfonyl fluoride to plasma reduced but did not eliminate the recovery of fibronectin fragments and likewise reduced the chemotactic activity. When the preparations were further purified by DEAE ion exchange and Sepharose 4B molecular sieve chromatography, however, intact fibronectin was recovered that lacked both chemotactic and chemokinetic activity. When fragment-poor fibronectin was allowed to sit at 25 degrees C in NaN3 but without protease inhibitors, increased fragmentation and increased chemotactic activity were noted. In addition, chemotactically active small m.w. fragments arose from high m.w. fragments or from intact fibronectin as demonstrated by rechromatography experiments over Sephadex G-150. These findings suggest that proteolytic cleavage of fibronectin during inflammatory processes produces fragments that selectively augment the recruitment of monocytes into tissue sites of inflammation.
D002478:Cells, Cultured; D002630:Chemotactic Factors; D002634:Chemotaxis, Leukocyte; D005353:Fibronectins / Q000502:physiology*; D006801:Humans; D007249:Inflammation / Q000503:physiopathology; D008214:Lymphocytes / Q000502:physiology; D009000:Monocytes / Q000502:physiology*; D009504:Neutrophils / Q000502:physiology; D010446:Peptide Fragments / Q000502:physiology
D002630:Chemotactic Factors; D005353:Fibronectins; D010446:Peptide Fragments