Anti-Macrophage monoclonal antibody [PE]

Schwann cells, the most abundant glial cells of the peripheral nervous system, represent the key players able to supply extracellular microenvironment for axonal regrowth and restoration of myelin sheaths on regenerating axons. Following nerve injury, Schwann cells respond adaptively to damage by acquiring a new phenotype. In particular, some of them localize in the distal stump to form the Bungner band, a regeneration track in the distal site of the injured nerve, whereas others produce cytokines involved in recruitment of macrophages infiltrating into the nerve damaged area for axonal and myelin debris clearance. Several neurotrophic factors, including pituitary adenylyl cyclase-activating peptide (PACAP), promote survival and axonal elongation of injured neurons. The present review summarizes the evidence existing in the literature demonstrating the autocrine and/or paracrine action exerted by PACAP to promote remyelination and ameliorate the peripheral nerve inflammatory response following nerve injury.

Currently available imaging techniques have limited specificity for the detection of active myocardial inflammation. Aluminum F-18-labeled 1,4,7-triazacyclononane-N,N',N''-triacetic acid conjugated folate (F-18-FOL) is a PET tracer targeting folate receptor beta (FR-beta), which is expressed on activated macrophages at sites of inflammation. We evaluated F-18-FOL PET for the detection of myocardial inflammation in rats with autoimmune myocarditis and studied the expression of FR-beta in human cardiac sarcoidosis specimens. Methods: Myocarditis was induced by immunizing rats (n = 18) with porcine cardiac myosin in complete Freund adjuvant. Control rats (n = 6) were injected with Freund adjuvant alone. F-18-FOL was intravenously injected, followed by imaging with a small-animal PET/CT scanner and autoradiography. Contrastenhanced high-resolution CT or F-18-FDG PET images were used for coregistration. Rat tissue sections and myocardial autopsy samples from 6 patients with cardiac sarcoidosis were studied for macrophages and FR-beta. Results: The myocardium of 10 of 18 immunized rats showed focal macrophage-rich inflammatory lesions, with FR-beta expression occurring mainly in M1-polarized macrophages. PET images showed focal myocardial F-18-FOL uptake colocalizing with inflammatory lesions (SUVmean, 2.1 +/- 1.1), whereas uptake in the remote myocardium of immunized rats and controls was low (SUVmean, 0.4 +/- 0.2 and 0.4 +/- 0.1, respectively; P<0.01). Ex vivo autoradiography of tissue sections confirmed uptake of F-18-FOL in myocardial inflammatory lesions. Uptake of F-18-FOL in inflamed myocardium was efficiently blocked by a nonlabeled FR-beta ligand folate glucosamine in vivo. The myocardium of patients with cardiac sarcoidosis showed many FR-beta-positive macrophages in inflammatory lesions. Conclusion: In a rat model of autoimmune myocarditis, F-18-FOL shows specific uptake in inflamed myocardium containing macrophages expressing FR-beta, which were also present in human cardiac sarcoid lesions. Imaging of FR-beta expression is a potential approach for the detection of active myocardial inflammation.