Disease relevance of Camp

• Here we analyzed CLP formation by core fusions with two distinct variants of the dimeric outer surface lipoprotein C (OspC) of the Lyme disease agent Borrelia burgdorferi [1].
• To assess this, thymocytes, bone marrow cells, or splenocytes (as a source of comparative nonhematopoietic cells) were harvested from C3H/HeN mice at 1, 4, or 24 hours after cecal ligation and puncture (CLP; to induce polymicrobial sepsis) or sham-CLP (Sham) [2].
• Increased mortality in the CLP/P. aeruginosa group was attributable to markedly impaired lung bacterial clearance and the early development of P. aeruginosa bacteremia [3].
• The importance of cathelicidins in antiviral skin host defense was confirmed by the observation of higher levels of HSV-2 replication in cathelicidin-deficient (Cnlp(-/-)) mouse skin (2.6 +/- 0.5 pg HSV/pg GAPDH, P < .05) compared with that seen in skin from their wild-type counterparts (0.9 +/- 0.3) [4].
• Therefore, more investigations are needed to confirm the toxicities and the therapeutic benefits of CAP18106-137 as an adjunctive therapy to antibiotics in the treatment of infections caused by gram-negative bacteria [5].

High impact information on Camp

• In this report we present the first evidence for a nonredundant regulator of this process, in that adult mice deficient in expression of the flt3 ligand (FL) have severely (10-fold) reduced levels of the CLP, accompanied by reductions in the earliest identifiable B and T cell progenitors [6].
• The first lineage commitment step of hematopoietic stem cells (HSC) results in separation into distinct lymphoid and myeloid differentiation pathways, reflected in the generation of common lymphoid and myeloid progenitors (CLP and CMP, respectively) [6].
• A new cadherin-like protein (CLP) was identified in oocytes, eggs, and cleavage stage embryos of Xenopus laevis [7].
• CLP was detected on the surface of stage 8 blastomeres by cell surface biotinylation, but only after the tight junctions of the blastula epithelium were opened by removal of Ca2+ [7].
• We conclude that CLP is a maternally encoded protein that is the major, if not only, cadherin-related protein present in the earliest stages of Xenopus development, and we propose that it may play a role in the Ca2(+)-dependent adhesion and junction formation between cleavage stage blastomeres [7].

Chemical compound and disease context of Camp

• Evaluation of antimicrobial and lipopolysaccharide-neutralizing effects of a synthetic CAP18 fragment against Pseudomonas aeruginosa in a mouse model [5].
• Select peptides of 15 to 21 residues, modeled on CAP18 (37 residues), retained activity against the gram-negative bacteria and methicillin-sensitive S. aureus, although the bactericidal activity was reduced compared to that of the parent peptide [8].
• In an accompanying study examining the acute effects of sepsis, organ injury at 18 hours after CLP as determined by histology and the degree of cell death by apoptosis were examined with the use of hematoxylin and eosin (H&E) and TUNEL staining and two-channel fluorescence-activated cell sorter (FACS) analysis [9].
• PURPOSE: To determine whether the survival curves and rates differ between a mutant strain of mice (C3H/HeJ: endotoxin-resistant) and an endotoxin-susceptible strain (C3H/HeN) when severe sepsis (caecal ligation and puncture: CLP) is performed with different anaesthetics (ketamine or varied exposure to halothane) [10].
• Sepsis (CLP) was induced in male NMRI mice that received either 0.9% saline, dopexamine (0.05 mg/kg/hour ip, DPX), the selective beta2-adrenergic antagonist ICI 118.551 (0.5 mg/kg ip every 12 hours, ICI) or a combination of both drugs [11].

Biological context of Camp

• This gene, named Cramp for cathelin-related antimicrobial peptide, was mapped to chromosome 9 at a region of conserved synteny to which genes for cathelicidins have been mapped in pig and man [12].
• The deletion of exons 5 and 6 in the AChE gene transforms anchored AChE into a soluble enzyme (Camp et al., 2004) [13].
• In mice, both CLP preparations induced high-titered antibody responses against the homologous OspC variant, but with substantial cross-reactivity against the other variant [1].
• This assay system provides a sensitive means of determining the Ly phenotypes of CLP to alloantigens or trinitrophenyl- (TNP) modified self antigens [14].
• In contrast, mice that overexpressed CuZn SOD did not differ in the amount of apoptosis after CLP compared with genetically normal mice (p = NS for all) [15].

Anatomical context of Camp

• Colon epithelial cell extracts from Cnlp+/+ mice had significantly greater antimicrobial activity against C. rodentium than those of mutant Cnlp-/- mice that lack mCRAMP [16].
• Cutting edge: mast cell antimicrobial activity is mediated by expression of cathelicidin antimicrobial peptide [17].
• A novel murine cathelin-like protein expressed in bone marrow [18].
• CLP was synthesized by large, late stage oocytes [7].
• In lymph node (LN), the frequency of CLP giving rise to clones specific for H-2d and H-2b is 1/480 and 1/860, respectively [19].

Associations of Camp with chemical compounds

• Treatment of CLP mice in vivo with either RU-38486 or PEG-(rsTNF-R1)2 was unable to reverse the increased A(o) in the bone marrow of these animals [2].
• CAP18 (cationic antimicrobial protein; 18 kDa) is a neutrophil-derived protein that can bind to and inhibit various activities of lipopolysaccharide (LPS) [5].
• To discriminate between the coagulation-independent protective TNF effect and a potential protective procoagulant TNF effect, formation of peritoneal adhesions after CLP was inhibited with heparin, hirudin, or urokinase [20].
• The addition of CAP18106-137 to aztreonam along with the bacteria did decrease the level of antibiotic-induced release of inflammatory mediators including tumor necrosis factor alpha, interleukin-6, and nitric oxide and also improved the survival of the mice [5].
• Under halothane anesthesia, the ceca were ligated with 4-0 silk suture and punctured twice with a 26-gauge needle (cecal ligation and puncture, CLP) [9].

Analytical, diagnostic and therapeutic context of Camp

• We found that the number of CLP reactive to alloantigens or TNP-modified self antigens were greatly reduced after treatment with either anti-Ly-1 or anti-Ly-2 serum and C in both C57BL/6 and CBA mice [14].
• Latently infected mice underwent a laparotomy with cecal ligation and puncture (CLP; n=30), a laparotomy alone (sham; n=10), or no surgery (control; n=5) [21].
• The intravenous injection of CpG ODN in mice that underwent CLP 12h earlier led to their increased cytokine production and their increased mortality [22].
• At 5 or 24 h after CLP (time points previously shown to be within the hyperdynamic and hypodynamic stage of sepsis, respectively, in the rat), cardiac output and blood flow in major organs were determined using a well-established radioactive microsphere method, and stroke volume and total peripheral resistance were calculated [23].
• In experiments reported here, we utilized a standard hindlimb crush injury and amputation in mice, followed in 24 hrs by polymicrobial septic challenge using cecal ligation and 23-gauge needle puncture (CLP) [24].

References