CXCL5 is required for angiogenesis, but not structural adaptation after small bowel resection

Abstract

Purpose: Intestinal adaptation is the compensatory response to massive small bowel resection (SBR) and characterized by lengthening of villi and deepening of crypts, resulting in increased mucosal surface area. Previous studies have demonstrated increased villus capillary blood vessel density after SBR, suggesting a role for angiogenesis in the development of resection-induced adaptation. Since we have previously shown enhanced expression of the proangiogenic chemokine CXCL5 after SBR, the purpose of this study was to determine the effect of disrupted CXCL5 expression on intestinal adaptation.

Methods: CXCL5 knockout (KO) and C57BL/6 wild type (WT) mice were subjected to either a 50% proximal SBR or sham operation. Ileal tissue was harvested on postoperative day 7. To assess for adaptation, villus height and crypt depth were measured. Submucosal capillary density was measured by CD31 immunohistochemistry.

Results: Both CXCL5-KO and WT mice demonstrated normal structural features of adaptation. Submucosal capillary density increased in the WT but not in the KO mice following SBR.

Conclusion: CXCL5 is required for increased intestinal angiogenesis during resection-induced adaptation. Since adaptive villus growth occurs despite impaired CXCL5 expression and enhanced angiogenesis, this suggests that the growth of new blood vessels is not needed for resection-induced mucosal surface area expansion following massive SBR.

Keywords: Adaptation; Angiogenesis; CXCL5; Intestine; Small bowel resection.

Figure 1

Adaptation occurs normally after 50% proximal small bowel resection (SBR) in both wild-type (WT) and CXCL5 knockout (KO) mice. Hematoxylin and eosin (H&E)-stained section of mouse ileum (magnification ×10) – A: WT sham operation. B: WT 50% proximal small bowel resection (SBR). C: CXCL5-KO sham operation. D: KO 50% proximal SBR with complete villus and crypt adaptive response.

Figure 2

Crypt depth and Villus height changes in response to 50% proximal small bowel resection (SBR) – Wild type (WT) and CXCL5 knock-out (KO) mice underwent either 50% SBR or sham operation (transection and reanastomosis of the bowel alone). On post operative day 7, the ileum was harvested and crypt depth and villus height were measured from H&E-stained sections. * = p < 0.05.

Figure 3

CD31-immunostaining of mouse ileum (magnification ×40) – A: Wild type (WT) sham operation. B: WT 50% proximal small bowel resection (SBR). C: CXCL5 knock-out (KO) sham operation. D: KO 50% proximal SBR. Arrows represent CD31+ stained blood vessels within the submucosa.

Figure 4

Quantification of submucosal capillary density – Wild type (WT) and CXCL5 knock-out (KO) mice underwent either 50% proximal small bowel resection (SBR) or sham operation (transection and reanastomosis of the bowel alone). On post operative day 7, the ileum was harvested and submucosal capillary density was measured from CD31-immunostained sections. * = p < 0.05.