Distinct chemotactic and angiogenic activities of peptides derived from Kaposi's sarcoma virus encoded chemokines.

R. Benelli, A. Barbero, A. Buffa, M. G. Aluigi, L. Masiello, L. Morbidelli, M. Ziche, A. Albini, D. Noonan

Research output: Contribution to journalArticle

Abstract

The vMIPs are chemokine-like proteins expressed by the Kaposi's sarcoma-associated herpesvirus (KSHV/HHV8) during the lytic phase of viral infection. vMIP-I activates CCR8, a chemokine receptor expressed by Th2 lymphocytes and cultured monocytes. vMIP-II is an agonist for CCR3, a receptor expressed by eosinophils, and an antagonist for several other chemokine receptors. Both are highly angiogenic in the chick chorio-allantoic membrane. We designed and tested three 26-mer peptides, derived from vMIP-I (pK-I), from vMIP-II (pK-II) and from the control MIP-1alpha (pM), spanning key residues of chemokines. pK-I, pK-II and pM all were able to activate a strong chemotactic response in monocytes, higher than parental vMIP-I and II. This corresponded to induction of calcium fluxes in these cells, typical of chemokines. Interestingly, pK-II and pM were also active on PMN neutrophils. In vivo studies (matrigel sponge and rabbit cornea models) showed that pK-I retains the strong angiogenic potential exerted by vMIP-I, while pK-II and pM induced an inflammatory response, probably mediated by PMN recruitment. Our observations indicate that chemokine-derived peptides can show biological activity at pharmacological concentrations. pK-I, in particular, displays the angiogenic activity of full-length vMIP-I, while all peptides appear to have acquired additional properties, stimulating new cellular targets.

Original languageEnglish
Pages (from-to)75-81
Number of pages7
JournalInternational Journal of Oncology
Volume17
Issue number1
Publication statusPublished - Jul 2000

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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