1.Ca2+ sensors modulate asthmatic symptoms in an allergic model for asthma.
Ten Broeke R1, Brandhorst MC, Leusink-Muis T, Villain M, De Clerck F, Blalock JE, Nijkamp FP, Folkerts G. Eur J Pharmacol. 2003 Aug 22;476(1-2):151-7.
We previously described two novel peptides, Ca2+-like peptide (CALP) 1 and CALP2, which interact with Ca2+-binding EF hand motifs, and therefore have the characteristics to define the role of the Ca2+-sensing regulatory protein calmodulin in asthma. In the present study, the effects of the calcium-like peptides were investigated in an animal model for allergic asthma. For that purpose, sensitized guinea pigs were intratracheally pretreated with CALP1 or CALP2. Thirty minutes later, the animals were challenged with aerosolized ovalbumin. Acute bronchoconstriction was measured as well as characteristic features of asthma 6 and 24 hours (h) after challenge. Neither CALP1 nor CALP2 prevented the anaphylactic response elicited by ovalbumin challenge. However, CALP1 pretreatment attenuated the influx of inflammatory cells in the lungs 6 h after challenge. Furthermore, radical production by these cells was diminished both 6 and 24 h after challenge.
2.Specific modulation of calmodulin activity induces a dramatic production of superoxide by alveolar macrophages.
Broeke RT1, Leusink-Muis T, Hilberdink R, Van Ark I, van den Worm E, Villain M, De Clerck F, Blalock JE, Nijkamp FP, Folkerts G. Lab Invest. 2004 Jan;84(1):29-40.
Airway inflammation is a characteristic feature in airway diseases such as asthma and chronic obstructive pulmonary disease. Oxidative stress, caused by the excessive production of reactive oxygen species by inflammatory cells like macrophages, eosinophils and neutrophils, is thought to be important in the complex pathogenesis of such airway diseases. The calcium-sensing regulatory protein calmodulin (CaM) binds and regulates different target enzymes and proteins, including calcium channels. In the present study, we investigated whether CaM, via the modulation of calcium channel function, influences [Ca(2+)](i) in pulmonary inflammatory cells, and consequently, modulates the production of reactive oxygen species by these cells. This was tested with a peptide termed calcium-like peptide 2 (CALP2), which was previously shown to regulate such channels. Specifically, radical production by purified broncho-alveolar lavage cells from guinea-pigs in response to CALP2 was measured.
