title: Mechanical stretch alters alveolar type II cell mediator release toward a proinflammatory pattern.
abstract: Increased mechanical stretch of alveolar type II (ATII) cells occurs during mechanical ventilation. The effects of three patterns of stretching rat ATII cells (frequency [min-1]-Deltasurface area [%]: S40-13, S60-13, S40-30) were compared with those in static cultures at 12, 18, and 24 h. Cell viability and expression of cyclooxygenase-2,5-lipoxygenase, inducible nitric oxide synthase (iNOS), and endothelial nitric oxide synthase (eNOS) were characterized. Supernatants were analyzed for eicosanoids, nitrite, cytokines, and stimulatory effects on rat lymphocytes. S40-13 simulates normal breathing; the other patterns increased amplitude and frequency. There were no significant differences between S40-13 and static cultures. S60-13 only significantly increased the supernatant nitrite (11.2+/-1.6 versus 3.9+/-0.4 microM at 24 h). S40-30 significantly reduced the number of trypan blue-excluding cells, increased the supernatant concentration of TXB2 (4.1+/-0.61 versus 2.2+/-0.36 pg/ml), 6-keto-PGF1alpha (8.7+/-1.0 versus 6.7+/-0.52 pg/ml), cysteinyl-LT (12.2+/-2.0 versus 6.1+/-0.75 pg/ml) and nitrite (7.2+/-1.7 versus 3.9+/-0.4 microM). S40-30 did not alter the release of tumor necrosis factor-alpha and monocyte chemotactic protein-1, but significantly reduced the concentration of the anti-inflammatory interleukin-10 (20.8+/-13.3 versus 130+/-21.5 pg/ml). Expression of cyclooxygenase-2/5-lipoxygenase was increased/decreased; expression of iNOS/eNOS was unchanged by high-amplitude stretch. Supernatants from S40-30 experiments caused lymphocyte activation measured by CD71 and CD54 surface expression. Continuing mechanical distension of ATII cells contributes to an inflammatory response by a shift in the balance of pro- and anti-inflammatory mediators.
authors.affiliation: Department of Respiratory Medicine and Critical Care, Universität Leipzig, Johannisallee 32, 04103 Leipzig, Germany. stefan.hammerschmidt@t-online.de
authors.forename: Stefan
authors.initials: S
authors.lastname: Hammerschmidt
authors.forename: Hartmut
authors.initials: H
authors.lastname: Kuhn
authors.forename: Ulrich
authors.initials: U
authors.lastname: Sack
authors.forename: Anke
authors.initials: A
authors.lastname: Schlenska
authors.forename: Christian
authors.initials: C
authors.lastname: Gessner
authors.forename: Adrian
authors.initials: A
authors.lastname: Gillissen
authors.forename: Hubert
authors.initials: H
authors.lastname: Wirtz
mesh_terms: D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics; D002470:Cell Survival; D051546:Cyclooxygenase 2; D016207:Cytokines / Q000096:biosynthesis; D015777:Eicosanoids / Q000096:biosynthesis; D015870:Gene Expression; D066298:In Vitro Techniques; D018836:Inflammation Mediators / Q000378:metabolism*; D007770:L-Lactate Dehydrogenase / Q000096:biosynthesis; D008213:Lymphocyte Activation; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis; D019001:Nitric Oxide Synthase / Q000235:genetics; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D011451:Prostaglandin-Endoperoxide Synthases / Q000235:genetics; D011650:Pulmonary Alveoli / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012121:Respiration, Artificial / Q000009:adverse effects / Q000379:methods; D013314:Stress, Mechanical
chemical_list: D016207:Cytokines; D015777:Eicosanoids; D018836:Inflammation Mediators; D009569:Nitric Oxide; D007770:L-Lactate Dehydrogenase; D001094:Arachidonate 5-Lipoxygenase; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases