PT  - JOURNAL ARTICLE
AU  - Coenjaerts, Frank E. J.
AU  - Walenkamp, Annemiek M. E.
AU  - Mwinzi, Pauline N.
AU  - Scharringa, Jelle
AU  - Dekker, Huberta A. T.
AU  - van Strijp, Jos A. G.
AU  - Cherniak, Robert
AU  - Hoepelman, Andy I. M.
TI  - Potent Inhibition of Neutrophil Migration by Cryptococcal Mannoprotein-4-Induced Desensitization
AID  - 10.4049/jimmunol.167.7.3988
DP  - 2001 Oct 01
TA  - The Journal of Immunology
PG  - 3988--3995
VI  - 167
IP  - 7
4099  - http://www.jimmunol.org/content/167/7/3988.short
4100  - http://www.jimmunol.org/content/167/7/3988.full
SO  - J. Immunol.2001 Oct 01; 167
AB  - Cryptococcal capsular Ags induce the production of proinflammatory cytokines in patients with cryptococcal meningitis. Despite this, their cerebrospinal fluid typically contains few neutrophils. Capsular glucuronoxylomannan is generally considered to mediate the inhibition of neutrophil extravasation. In the current study, culture supernatant harvested from the nonglucuronoxylomannan-producing strain CAP67 was found to be as potent as supernatant from wild-type strains in preventing migration. We identified capsular mannoprotein (MP)-4 as the causative agent. Purified MP-4 inhibited migration of neutrophils toward platelet-activating factor, IL-8, and fMLP, probably via a mechanism involving chemoattractant receptor cross-desensitization, as suggested by its direct chemotactic activity. Supporting this hypothesis, MP-4 elicited Ca2+ transients that were inhibited by preincubation with either fMLP, IL-8, or C5a, but not platelet-activating factor, and vice versa. Moreover, MP-4 strongly decreased the neutrophil surface expression of L-selectin and induced shedding of TNF receptors p55/p75, whereas CD11b/18 increased. Finally, MP-4 was clearly detectable in both serum and cerebrospinal fluid of patients suffering from cryptococcal meningitis. These findings identify MP-4 as a novel capsular Ag prematurely activating neutrophils and desensitizing them toward a chemoattractant challenge.