Chemical Association via Exact Thermodynamic Formulations

It can be fruitful to view two-component physical systems of attractive monomers, A and B, ``chemically'' in terms of a reaction A + B C, where C = AB is an associated pair or complex. We show how to construct free energies in the three-component or chemical picture which, under mass-action equilibration, exactly reproduce any given two-component or ``physical'' thermodynamics. Order-by-order matching conditions and closed-form chemical representations reveal the freedom available to modify the A-C, B-C, and C-C interactions and to adjust the association constant. The theory (in the simpler one-component, i.e., A = B, case) is illustrated by treating a van der Waals fluid.Comment: 15 double-spaced pages (RevTeX), including 1 eps figur

Native A1AT effect on efferocytosis receptors expression and ADAM-17 (TACE) activity in CS-exposed AM.

<p><b>A-B.</b> Representative immunoblot (<b>A</b>) and densitometry (<b>B</b>, n = 4) of MAR expression in CS-exposed (3%, 4 h) and A1AT-treated (Aralast NP, 100 μg/mL, 16 h) primary rat AM. 1-way ANOVA, Sidak’s multiple comparisons test, * p<0.05. <b>C.</b> Representative immunoblots (n = 4) of MAR expression in human AM isolated from the BAL of non-smoker and smoker individuals prior and after <i>ex-vivo</i> A1AT treatment (Prolastin C, 100 μg/mL, 16 h). <b>D.</b> A1AT treatment (Prolastin C, 100 μg/mL) time-dependently decreases TACE activity in the CS-exposed (10%, 4 h) THP-1 membrane fraction. <b>E.</b> Representative immunoblot of MAR expression in the CS-exposed THP-1 cell lysates and supernatants after treatment with A1AT (Prolastin C, 100 μg/mL, 30 min) or with a pharmacological inhibitor of TACE (TAPI-1, 50 μM, 30 min). <b>F</b>. Representative immunoblot of MAR expression in the CS-exposed NR8383 AM cell lysates and supernatants after A1AT treatment (Prolastin C, 100 μg/mL, 16 h). The results are representative of 3 independent experiments. <b>G-H.</b> Representative immunoblot (<b>G</b>) and densitometry (<b>H</b>, n = 4) of PSR expression in CS-exposed (10%, 4 h) and A1AT-treated (Aralast NP, 100 μg/mL, 16 h) NR8383 AM membrane fractions. <b>I.</b> Representative immunoblots (n = 3) of PSR and SRB-2 expression in PiZZ-AM (13 μg protein equally loaded in each lane) after A1AT augmentation therapy (Zemaira, CSL Behring, 60 mg/kg single dose or 120 mg/kg double dose). Note that doubling the weekly A1AT dose (visit 2) increases PiZZ-AM A1AT intracellular abundance and PSR and SRB-2 expression levels vs. A1AT single dose (visit 1), effect that persist as carried over effect after resuming single A1AT dose (visit 3).</p

Native A1AT effect on CS-exposed AM phagocytosis and global scavenging function following concomitant Fc-coated and apoptotic targets exposure.

<p><b>A-B.</b> Relative phagocytosis index representing % of primary rat AM that engulfed fluorescently labeled Fc-coated targets after CS-exposure (10%, 4 h) and A1AT treatment (Aralast NP, 100 μg/mL, 4 h), compared to AM engulfment in control media. 1-way ANOVA, Sidak’s multiple comparisons test, * p<0.05. Note the lack of significant effect on phagocytosis at baseline (AC) or during CS-exposure following 16 h of A1AT treatment. <b>B-C</b>. iNOS expression (<b>B</b>) and TNF-α secretion (<b>C</b>) in primary rat AM exposed to CS (3%, 4 h) and treated with LPS (100 ng/mL, 4 h) and A1AT (Aralast NP, 100 μg/mL, 4 h). <b>D.</b> Higher Fc-coated to apoptotic targets ratio (0:1 to 10:1) dose-dependently inhibits NR8383 AM efferocytosis. <b>E.</b> Higher mouse anti-human CD3⁺ CTG-labeled Jurkat T-cells (Fc-coated targets) to apoptotic targets ratio (0:1 to 5:1) dose-dependently inhibits primary rat AM efferocytosis. <b>F.</b> Higher apoptotic to Fc-coated targets ratio (0:1 to 24:1) dose-dependently inhibits NR8383 AM phagocytosis. <b>G.</b> Overall engulfment [efferocytosis (E), phagocytosis (P), and efferocytosis + phagocytosis (E+P)] of CS-exposed and A1AT-treated (Aralast NP, 100 μg/mL, 16 h) primary rat AM when concomitantly exposed to apoptotic and Fc-coated targets at 1:1 ratio. 1-way ANOVA, Sidak’s multiple comparisons test, * p<0.05. Data are presented as mean ± SEM.</p

Native and polymerized A1AT <i>ex-vivo</i> effect on CS-exposed AM efferocytosis.

<p><b>A</b>. Absolute efferocytosis index representing % of cells that engulfed fluorescently labeled apoptotic targets among AM isolated from active smokers (dark circles) compared to those from healthy non-smokers (light gray circles). Native A1AT (Aralast NP, 100 μg/mL, 16 h) significantly increased efferocytosis in AM from smokers (dark gray circles), but not in those from healthy non-smokers (gray squares). 1-way ANOVA, Sidak’s multiple comparisons test, * p<0.05. <b>B-C</b>. Relative efferocytosis index representing % of AM that engulfed fluorescently labeled apoptotic targets following indicated exposures, when compared to those exposed to control media. Primary rat AM (<b>B</b>) or NR8383 AM (<b>C</b>) were exposed <i>ex-vivo</i> to AC or CS (4h, 3% or 10%, respectively, 4 h), native A1AT (Aralast NP, 100 μg/mL, 16 h), and compared to IL-4 (20 ng/mL, 72 h). <b>D</b>. Polymerized A1AT (Aralast NP, 100 μg/mL, 16h) has no effect on CS-exposed NR8383 AM efferocytosis. Data are presented as mean ± SEM, 1-way ANOVA, Sidak’s multiple comparisons test, * p<0.05, ** p<0.001, *** p<0.0001.</p