Background-Induction of matrix metalloproteinases (MMPs) contributes to adverse remodeling after myocardial infarction (MI). Whether a region-and type-specific distribution of MMPs occurs within the post-MI myocardium remained unknown. Methods and Results-Ten sheep were instrumented with a sonomicrometry array to measure dimensions in 7 distinct regions corresponding to the remote, transition, and MI regions. Eight sheep served as reference controls. The relative abundance of representative MMP types and the tissue inhibitors of the MMPs (TIMPs) was quantified by immunoblotting. Segment length increased from baseline in the remote (24.9Ϯ5.4%), transition (18.0Ϯ2.9%), and MI (53.8Ϯ11.0%) regions at 8 weeks after MI (PϽ0.05) and was greatest in the MI region (PϽ0.05). Region-and type-specific changes in MMPs occurred after MI. For example, MMP-1 and MMP-9 abundance was unchanged in the remote, fell to 3Ϯ2% in the transition, and was undetectable in the MI region (PϽ0.05). MMP-13, MMP-8, and MT1-MMP increased by Ͼ300% in the transition and MI regions (PϽ0.05). TIMP abundance decreased significantly in the transition region after MI and fell to undetectable levels within the MI region. Conclusions-The unique findings of this study were 2-fold. First, changes in regional geometry after MI were associated with changes in MMP levels. Second, a region-specific portfolio of MMPs was induced after MI and was accompanied by a decline in TIMP levels, indicative of a loss of MMP inhibitory control. Targeting the regional imbalance between specific MMPs and TIMPs within the post-MI myocardium holds therapeutic potential.

IgA immunoblasts can seed both intestinal and nonintestinal mucosal sites following localized mucosal immunization, an observation that has led to the concept of a common mucosal immune system. In this study, we demonstrate that the mucosae-associated epithelial chemokine, MEC (CCL28), which is expressed by epithelia in diverse mucosal tissues, is selectively chemotactic for IgA Ab-secreting cells (ASC): MEC attracts IgA- but not IgG- or IgM-producing ASC from both intestinal and nonintestinal lymphoid and effector tissues, including the intestines, lungs, and lymph nodes draining the bronchopulmonary tree and oral cavity. In contrast, the small intestinal chemokine, TECK (CCL25), attracts an overlapping subpopulation of IgA ASC concentrated in the small intestines and its draining lymphoid tissues. Surprisingly, T cells from mucosal sites fail to respond to MEC. These findings suggest a broad and unifying role for MEC in the physiology of the mucosal IgA immune system.

The accumulation of immunoglobulin (Ig)A antibody-secreting cells (ASCs) in the lactating mammary gland leads to secretion of antibodies into milk and their passive transfer to the suckling newborn. This transfer of IgA from mother to infant provides transient immune protection against a variety of gastrointestinal pathogens. Here we show that the mucosal epithelial chemokine CCL28 is up-regulated in the mammary gland during lactation and that IgA ASCs from this tissue express CCR10 and migrate to CCL28. In vivo treatment with anti-CCL28 antibody blocks IgA ASC accumulation in the mammary gland, inhibiting IgA antibody secretion into milk and the subsequent appearance of antibody in the gastrointestinal tract of nursing neonates. We propose that CCL28 is a key regulator of IgA ASC accumulation in the mammary gland and thus controls the passive transfer of IgA antibodies from mother to infant.