Cryptococcal glucuronoxylomannan induces interleukin (IL)-8 production by human microglia but inhibits neutrophil migration toward IL-8

Myriam M. Lipovsky, Genya Gekker, Shuxian Hu, Laura C. Ehrlich, Andy I.M. Hoepelman, Phillip K. Peterson

Research output: Contribution to journalArticlepeer-review

60 Scopus citations

Abstract

On the basis of the clinical observation that the cerebrospinal fluid (CSF) of patients with cryptococcal meningitis contains high levels of the chemokine interleukin (IL)-8 but few polymorphonuclear leukocytes (PMNL), the production of IL-8 by cultured brain glial cells after stimulation with two serotypes of cryptococcal capsular polysaccharide glucuronoxylomannan (GXM) was studied, followed by an assessment of the effect of GXM on PMNL migration toward IL-8. GXM serotype A but not D was capable of inducing IL-8 production in human fetal microglial cell but not in astrocyte cultures. When added directly to the PMNL, GXM (both serotypes) potently blocked PMNL migration toward IL-8. The mechanism of GXM's inhibitory effect appeared to involve cross-desensitization. These findings suggest that GXM can induce IL-8 production in the brain but that GXM in the systemic circulation inhibits migration of PMNL toward IL-8.

Original languageEnglish (US)
Pages (from-to)260-263
Number of pages4
JournalJournal of Infectious Diseases
Volume177
Issue number1
DOIs
StatePublished - 1998

Bibliographical note

Funding Information:
Human brain tissue was obtained under a protocol approved by the Human Subjects Research Committee of Hennepin County Medical Center. Informed consent was obtained for fetal brain tissue from patients who were undergoing elective abortions and for peripheral blood leukocytes from healthy human volunteers prior to donation. Financial support: NIH (DA-04381, DA-09924).

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