Role of the chemokines CCL3/MIP-1 alpha and CCL5/RANTES in sponge-induced inflammatory angiogenesis in mice.
OBJECTIVE
We examined the potential contribution of CCL3 and CCL5 to inflammatory angiogenesis in mice.


METHODS
Polyester-polyurethane sponges were implanted in mice and blood vessel counting and hemoglobin, myeloperoxidase and N-acetylglucosaminidase measurements used as indexes for vascularization, neutrophil and macrophage accumulation, respectively.


RESULTS
CCL3 and CCL5 were expressed throughout the observation period. Exogenous CCL3 enhanced angiogenesis in WT, but angiogenesis proceeded normally in CCL3(-/-) mice, suggesting that endogenous CCL3 is not critical for sponge-induced angiogenesis in mice. CCL5 expression was detected at day 1, but levels significantly increased thereafter. Exogenous CCL5 reduced angiogenesis in WT mice possible via CCR5 as CCL5 was without an effect in CCR5(-/-) mice. Treatment of WT with the CCR1/CCR5 antagonist, Met-RANTES, prevented neutrophil and macrophage accumulation, but enhanced sponge vascularization.


CONCLUSIONS
Thus, endogenous CCL3 appears not to play a role in driving sponge-induced inflammatory angiogenesis in mice. The effects of CCL5 were anti-angiogenic and appeared to be mediated via activation of CCR5.
Barcelos
Lucíola S
LS
Department of Fisiologia e Biofísica, ICB, UFMG, Belo Horizonte, Brazil. aloicul@yahoo.com
Coelho
Amanda M
AM
Russo
Remo C
RC
Guabiraba
Rodrigo
R
Souza
Adriano L S
AL
Bruno-Lima
Guilherme
G
Proudfoot
Amanda E I
AE
Andrade
Sílvia P
SP
Teixeira
Mauro M
MM
D000818:Animals; D054405:Chemokine CCL3 / Q000235:genetics / Q000378:metabolism*; D018946:Chemokine CCL5 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007249:Inflammation / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018919:Neovascularization, Physiologic; D011994:Recombinant Proteins / Q000378:metabolism; D015503:Surgical Sponges / Q000009:adverse effects*; D013997:Time Factors
D054405:Chemokine CCL3; D018946:Chemokine CCL5; C108335:RANTES, Met-; D011994:Recombinant Proteins