Wound healing in MIP-1alpha(-/-) and MCP-1(-/-) mice - PubMed (original) (raw)
Comparative Study
Wound healing in MIP-1alpha(-/-) and MCP-1(-/-) mice
Q E Low et al. Am J Pathol. 2001 Aug.
Abstract
A salient feature of normal wound healing is the development and resolution of an acute inflammatory response. Although much is known about the function of inflammatory cells within wounds, little is known about the chemotactic and activation signals that influence this response. As the CC chemokines macrophage inflammatory protein-1alpha (MIP-1alpha) and monocyte chemotactic protein-1 (MCP-1) are abundant in acute wounds, wound repair was examined in MIP-1alpha(-/-) and MCP-1(-/-) mice. Surprisingly, wound re-epithelialization, angiogenesis, and collagen synthesis in MIP-1alpha(-/-) mice was nearly identical to wild-type controls. In contrast, MCP-1(-/-) mice displayed significantly delayed wound re-epithelialization, with the greatest delay at day 3 after injury (28 +/- 5% versus 79 +/- 14% re-epithelialization, P < 0.005). Wound angiogenesis was also delayed in MCP-1(-/-) mice, with a 48% reduction in capillary density at day 5 after injury. Collagen synthesis was impeded as well, with the wounds of MCP-1(-/-) mice containing significantly less hydroxyproline than those of control mice (25 +/- 3 versus 50 +/- 8 microg/wound at day 5, P < 0.0001). No change in the number of wound macrophages was observed in MCP-1(-/-) mice, suggesting that monocyte recruitment into wounds is independent of this chemokine. The data suggest that MCP-1 plays a critical role in healing wounds, most likely by influencing the effector state of macrophages and other cell types.
Figures
Figure 1.
Histological comparison of wounds from C57BL/6 controls (A and B), MCP-1−/− (C and D), and MIP-1α−/− (E and F) mice on day 3 (A, C, and E) and day 5 (B, D, and F) after injury. H&E-stained sections were photographed at ×25 power. The wound margins are indicated by upward arrows. In C and D, the margins of the advancing epithelial layer are indicted by downward arrowheads. By 3 days after injury, most wounds from control and MIP-1α−/− mice showed complete re-epithelialization (A and E). In contrast, day 3 wounds from MCP-1−/− mice showed delayed re-epithelialization (C). At day 5, wounds from MCP-1−/− mice still exhibited incomplete re-epithelialization (D).
Figure 2.
Effects of MIP-1α deficiency on dermal wound repair. A: Determination of wound angiogenesis in MIP-1α−/− mice. Vessel density was measured in wounds at 5 and 7 days after injury. CD31-stained tissues were analyzed by image analysis and CD31+ areas quantified and compared to total wound area (100%). Data are expressed as mean ± SEM (n = 4). B: Determination of wound hydroxyproline content as an indicator of collagen levels. Hydroxyproline content per wound (±SEM) was measured at days 5 and 7 after injury. Day 5, n = 4 for C57BL/6 and n = 6 for MIP-1α−/−. Day 7, n = 4 for both strains.
Figure 3.
Effects of MCP-1 deficiency on dermal wound repair. A: Time course of re-epithelialization in MCP-1−/− mice compared to wild-type controls. Percent re-epithelialization (±SEM) is shown [n = 6 (days 1 to 14), n = 4 (day 21)]. P < 0.0001 between groups by two-way analysis of variance. B: Time course of wound angiogenesis in MCP-1−/− mice. Blood vessel density (±SEM) is shown (n = 6). P < 0.02 between groups by two-way analysis of variance. C: Collagen content of wounds from MCP-1−/− mice. As an indicator of collagen amount, hydroxyproline content (±SEM) of wounds was determined. [n = 6 (days 1 to 10), n = 4 (day 21)]. P < 0.05 between groups by two-way analysis of variance.
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