Dataset Information

Expression of the chemokine binding protein M3 promotes marked changes in the accumulation of specific leukocytes subsets within the intestine.

ABSTRACT: Chemokines are small proteins that direct leukocyte trafficking under homeostatic and inflammatory conditions. We analyzed the differential expression of chemokines in distinct segments of the intestine and investigated the importance of chemokines for the distribution of leukocytes in the intestine during homeostatic and inflammatory conditions.We analyzed messenger RNA for all known chemokines in different segments of the gut by quantitative polymerase chain reaction. To study the effect of multiple-chemokine blockade in the gut, we generated transgenic mice that expressed the chemokine binding protein M3 in the intestine (V-M3 mice). We used flow cytometry to evaluate the changes in the numbers of leukocytes.We observed distinct chemokine expression profiles in the 6 segments of the gut. Some chemokines were expressed throughout the intestine (CCL28, CCL6, CXCL16, and CX3CL1), whereas others were expressed preferentially in the small (CCL25 and CCL5) or large intestine (CCL19, CCL21, and CXCL5). Expression of the chemokine blocker M3 in intestinal epithelial cells resulted in reduced numbers of B and T cells in Peyer's patches, reduced numbers of intraepithelial CD8alphabeta(+)/TCRalphabeta(+) and CD8alphaalpha(+)/TCRalphabeta(+) T cells, and reduced numbers of lamina propria CD8(+) T cells. Strikingly, M3 expression markedly reduced the number of eosinophils and macrophages in the small and large intestines. Dextran sulfate sodium treatment of control mice led to marked changes in the expression of chemokines and in the number of myeloid cells in the colon. These cellular changes were significantly attenuated in the presence of M3.Our study reveals a complex pattern of chemokine expression in the intestine and indicates that chemokines are critical for leukocyte accumulation in the intestine during homeostasis and inflammation.

SUBMITTER: Shang L

PROVIDER: S-EPMC2736321 | biostudies-literature | 2009 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Expression of the chemokine binding protein M3 promotes marked changes in the accumulation of specific leukocytes subsets within the intestine.

Shang Limin L Thirunarayanan Nanthakumar N Viejo-Borbolla Abel A Martin Andrea P AP Bogunovic Milena M Marchesi Federica F Unkeless Jay C JC Ho Yin Y Furtado Glaucia C GC Alcami Antonio A Merad Miriam M Mayer Lloyd L Lira Sergio A SA

Gastroenterology 20090606 3

<h4>Background & aims</h4>Chemokines are small proteins that direct leukocyte trafficking under homeostatic and inflammatory conditions. We analyzed the differential expression of chemokines in distinct segments of the intestine and investigated the importance of chemokines for the distribution of leukocytes in the intestine during homeostatic and inflammatory conditions.<h4>Methods</h4>We analyzed messenger RNA for all known chemokines in different segments of the gut by quantitative polymerase ...[more]

PMID: 19501588

Similar Datasets

Project description:Chemokines are important in macrophage recruitment and the progression of atherosclerosis. The 'M3' chemokine binding protein inactivates key chemokines involved in atherosclerosis (e.g. CCL2, CCL5 and CX3CL1). We aimed to determine the effect of M3 on plaque development and composition. In vitro chemotaxis studies confirmed that M3 protein inhibited the activity of chemokines CCL2, CCL5 and CX3CL1 as primary human monocyte migration as well as CCR2-, CCR5- and CX3CR1-directed migration was attenuated by M3. In vivo, adenoviruses encoding M3 (AdM3) or green fluorescence protein (AdGFP; control) were infused systemically into apolipoprotein (apo)-E-/- mice. Two models of atherosclerosis development were used in which the rate of plaque progression was varied by diet including: (1) a 'rapid promotion' model (6-week high-fat-fed) and (2) a 'slow progression' model (12-week chow-fed). Plasma chemokine activity was suppressed in AdM3-infused mice as indicated by significantly less monocyte migration towards AdM3 mouse plasma ex vivo (29.56%, p = 0.014). In the 'slow progression' model AdM3 mice had reduced lesion area (45.3%, p = 0.035) and increased aortic smooth muscle cell α-actin expression (60.3%, p = 0.014). The reduction in lesion size could not be explained by changes in circulating inflammatory monocytes as they were higher in the AdM3 group. In the 'rapid promotion' model AdM3 mice had no changes in plaque size but reduced plaque macrophage content (46.8%, p = 0.006) and suppressed lipid deposition in thoracic aortas (66.9%, p<0.05). There was also a reduction in phosphorylated p65, the active subunit of NF-κb, in the aortas of AdM3 mice (37.3%, p<0.0001). M3 inhibited liver CCL2 concentrations in both models with no change in CCL5 or systemic chemokine levels. These findings show M3 causes varying effects on atherosclerosis progression and plaque composition depending on the rate of lesion progression. Overall, our studies support a promising role for chemokine inhibition with M3 for the treatment of atherosclerosis.

Dataset Information

Expression of the chemokine binding protein M3 promotes marked changes in the accumulation of specific leukocytes subsets within the intestine.

Publications

Expression of the chemokine binding protein M3 promotes marked changes in the accumulation of specific leukocytes subsets within the intestine.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets