Suppression of leukocyte chemotaxis by human IgA myeloma components.

Abstract

Materials and MethodsCell Preparation, Chemotaxis, and Random Mobility. Human polymorphonuclear leukocytes (PMNs) were prepared from peripheral blood of healthy adult donors. Blood was mixed with heparin, 10 U/ml, to prevent coagulation. Neutrophil preparations were obtained as previously described (2, 5-7) by Plasmagel sedimentation of erythrocytes and resuspension of leukocytes to a concentration of 7 x 106 PMNs/ml in Hanks' balanced salt solution (HBSS). In some experiments mononuclear cells were removed from these preparations by Ficoll-Hypaque centrifugation (8). Cell suspensions obtained by this combined technique contained greater than 95% PMNs. Monocytos were prepared by Ficoll-Hypaque centrifugation of whole blood (8), and the band ofmononuclear cells was collected, washed, and adjusted to a cell concentration of 5 x l0 s cells per ml with HBSS. This preparation contained from 11 to 40% monocytes as determined by peroxidase staining (9).Studies of PMN chemotaxis were performed using a modified Boyden technique (2, 5-7). Chemotaxis was expressed as a chemotactic index representing the average number of cells per high power field (400 ×) which had migrated to the distal side of the membrane. Monocyte chemotaxis was measured in a similar type of chamber with a 5 fern pore size Nuclepore membrane (Nuclepore Corp., Pleasanton, Calif.) (10). In some PMN experiments a slightly different Boyden type chamber was used (11) so that the lower compartment could be aspirated and the number of cells which had migrated into the lower chamber counted.Random PMN mobility was assessed using the capillary tube migration assay (12). PMNs were isolated by combined plasmagel sedimentation and Ficoll-Hypaque centrifugation. Capillary *

FcαRI (CD89) Alleles Determine the Proinflammatory Potential of Serum IgA

“…As noted, some studies have suggested an anti-inflammatory function for IgA and Fc␣RI, as demonstrated in the suppression of neutrophil chemotaxis, down-regulation of the generation of reactive oxygen species, and the induction of the anti-inflammatory cytokine IL-1ra (32,34). Because IgA in the serum does not fix complement by the classical pathway, IgA is thought to act as a "discrete housekeeper" in which foreign Ags are incorporated into immune complexes by IgA and removed by the phagocytic system, with little or no resultant inflammation (57).…”

“…Unlike Fc␥RIII and Fc RI, however, Fc␣RI is often expressed in the absence of ␥-chain pairing (26,27) and the function of this nonpaired Fc␣RI has not been defined. Indeed, the net function of Fc␣RI per se is unresolved, with some investigators reporting a capacity to initiate a proinflammatory program (28 -30) while others report a noninflammatory profile (31)(32)(33)(34)(35)(36).…”

Serum Inhibitor of C5 Fragment-Mediated Polymorphonuclear Leukocyte Chemotaxis Associated with Chronic Hemodialysis

“…A modification of the Boyden technique with 5-,um pore size membranes (Sartorius Filters, Inc., S. San Francisco, Calif.) to separate the upper cell suspension compartment and the lower chemotactic factor compartment was used to assess PMN chemotaxis (16). The PMN suspension, 0.4 ml at 7.0 x 106 PMN/ml, was placed in the upper compartment and chemotactic factor plus a 10% serum test sample in the lower 0.25 ml compartment.…”

Dysfunctions of the Iga system: a common link between intestinal and renal diseases

“…37 We have demonstrated for the first time that monovalent targeting of FcaRI by mIgA inhibits IgG-mediated phagocytosis in human monocytes, 30 which explains the previously reported inhibitory functions of serum mIgA. [23][24][25][27][28][29] More importantly, we have been able to show that FcaRI-mediated inhibition is not mediated by conventional inhibitory motifs such as the immunoreceptor tyrosine-based inhibition motif. While c-less FcaRI recycles mIgA, thus playing an essential role in mIgA homeostasis, FcRc-associated FcaRI mediates either activating or inhibitory responses.…”

“…22 Several groups have demonstrated that in the absence of antigen, serum IgA downregulates IgG-mediated phagocytosis, chemotaxis, bactericidal activity, oxidative burst activity and cytokine release. [23][24][25][26][27][28][29] These IgA monomers may initiate FcaRImediated non-inflammatory responses against bacteria that breach the mucosal barrier. 30 Another piece of data supporting the inhibitory role of serum mIgA is the observation that selective IgA-deficient patients frequently present allergies and autoimmunity.…”