Inhibition of neutrophil chemotaxis by elastase-generated IgG fragments.
IgG1 is cleaved in vitro by granulocyte elastase into Fc and Fab fragments. The elastase-specific Fc fragment has been previously detected in vivo. Biological activity of the fragments has been described in modulating neutrophil oxidative metabolism and enzyme release. To investigate further effects granulocyte chemotaxis (CT) was tested. The CT was assayed in Boyden chambers and the chemotactic index (CI) was calculated which represents the mean distance travelled by the activated cells. Stimulation of leucocyte CT by casein, activated serum and FMLP gives maximal values of delta CI = 46.7, 26.4 and 7.2 microns, respectively. Native IgG1 and the elastase-produced IgG fragments do not stimulate leucocyte CT. FMLP-stimulated CT is specifically inhibited by the elastase-produced Fc fragments. Addition of 7 nmol Fc to stimulus concentrations of 16 to 125 nM FMLP results in total inhibition of chemotaxis demonstrated by CI values which are lower than those for unstimulated cells. The inhibition of CT is concentration dependent in the range of 2 to 7 nmol Fc/10(6) PMN. Number and affinity of FMLP receptors are not influenced by Fc fragments, so Fc binds neither to FMLP nor the FMLP receptor. CT stimulated by casein shows a large portion of chemokinesis. Only at suboptimal casein concentrations do Fc and IgG have an inhibitory effect on CT (0.63 mg casein/ml, 10 nmol peptide/10(6) PMN). C5a-stimulated CT is not influenced by IgG or IgG fragments which indicates that the samples are not cytotoxic. So the FMLP and casein-stimulated CT is specifically inhibited by the elastase-produced Fc fragments in a low concentration range.
Eckle
I
I
Centre for Internal Medicine, Philipps University, Marburg, Germany.
Kolb
G
G
Havemann
K
K
D001665:Binding Sites; D002364:Caseins / Q000494:pharmacology; D002634:Chemotaxis, Leukocyte / Q000187:drug effects*; D015936:Complement C5a / Q000494:pharmacology; D006801:Humans; D007128:Immunoglobulin Fragments / Q000032:analysis / Q000494:pharmacology*; D007074:Immunoglobulin G / Q000737:chemistry; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000276:immunology; D010196:Pancreatic Elastase / Q000494:pharmacology*; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic / Q000502:physiology
D002364:Caseins; D007128:Immunoglobulin Fragments; D007074:Immunoglobulin G; D044042:Receptors, Formyl Peptide; D011971:Receptors, Immunologic; D009240:N-Formylmethionine Leucyl-Phenylalanine; D015936:Complement C5a; D010196:Pancreatic Elastase