Adhesion and activation of human neutrophils on basement membrane molecules

In a previous study, we found that type I collagen activates human polymorphonuclear neutrophils by binding to a membrane integrin [3]. The activation depends on two sequences, both contained in the alpha 1 (I) CB6 peptide, one is RGD, starting at residue 915, and the second is DGGRYY, starting at residue 1034 of the alpha 1(I) chain. We checked the effect of several other types of collagens, principally type IV collagen from several origins. The basement membrane from bovine lens as well as type IV collagen prepared from it by tartaric acid extraction did not activate the human neutrophils. In contrast, when neutrophils had been previously in contact with type IV collagen their activation by type I or the alpha 1(I) CB6 peptide, or the bacterial peptide N-formyl-methionyl-leucyl-phenylalanine, was inhibited. This effect was abolished when type IV collagen had been previously treated by pepsin. On the other hand, the fractions of type IV collagen that resisted digestion by bacterial collagenase still exhibited this inhibiting effect. This effect probably explains the physiological property of neutrophils to cross vascular walls without being activated.