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Enhanced production of IGF-I in the lungs of fibroproliferative ARDS patients.

Andonegui G, Krein PM, Mowat C, Brisebois R, Doig C, Green FH, Léger C, Winston BW - Physiol Rep (2014)

Bottom Line: Our data show that IGF-I is significantly increased in the ELF in FP-ARDS patients.A significant correlation between IGF-I and PCP-III in the ELF of FP-ARDS patients is found.Our data suggest that IGF-I found in the lungs of FP-ARDS patients results from both increased lung permeability and local production of IGF-I.

View Article: PubMed Central - PubMed

Affiliation: Department of Critical Care Medicine, Faculty of Medicine, University of Calgary Health Research Innovation Center, Calgary, Alberta, Canada Immunology Research Group, Faculty of Medicine, University of Calgary Health Research Innovation Center, Calgary, Alberta, Canada.

No MeSH data available.


Related in: MedlinePlus

Albumin Levels in ELF and Serum. (A) Serum albumin levels are decreased in FP‐ARDS individuals (n = 12) versus controls (n = 10), *P < 0.01, 95% CI. (B) ELF albumin levels were calculated by measuring BALF albumin levels and normalizing BALF dilution by the urea method as described in the Materials and Methods. Results show increased albumin in FP‐ARDS (n = 14) versus control (n = 11), *P < 0.01, 95% CI. (C) A significant positive relationship exists between free IGF‐I and albumin levels in the ELF of the prospective BAL populations, P < 0.01, 95% CI using Spearman Rank Correlation.
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fig04: Albumin Levels in ELF and Serum. (A) Serum albumin levels are decreased in FP‐ARDS individuals (n = 12) versus controls (n = 10), *P < 0.01, 95% CI. (B) ELF albumin levels were calculated by measuring BALF albumin levels and normalizing BALF dilution by the urea method as described in the Materials and Methods. Results show increased albumin in FP‐ARDS (n = 14) versus control (n = 11), *P < 0.01, 95% CI. (C) A significant positive relationship exists between free IGF‐I and albumin levels in the ELF of the prospective BAL populations, P < 0.01, 95% CI using Spearman Rank Correlation.

Mentions: As we detected high levels of IGF‐I in the serum of the early ALI/ARDS population, we sought to determine whether the lung IGF‐I protein increase in the FP‐ARDS population was the result of local production or the result of leakage of IGF‐I from the serum through increased lung permeability. First, we measured the levels of albumin in the ELF and serum samples from our prospective patient populations, as previously described Rennard et al. (1986). As shown in Fig. 4A, albumin levels are decreased in the serum of our FP‐ARDS patients whereas albumin levels normalized for BALF dilution are significantly increased in the ELF of FP‐ARDS patients compared to controls (Fig. 4B). These results suggest a significantly increased permeability of the epithelial:endothelial barrier in the lungs of FP‐ARDS patients. Figure 4C shows a significant positive relationship between free IGF‐I and albumin in the ELF (P < 0.01) of FP‐ARDS patients which suggests that the elevated IGF‐I protein in the ELF could in fact be derived from the serum, and arrives in the lung via vascular leak. However, this is not the case as when albumin levels were used to account for serum leak in the patient lungs, the FP‐ARDS population still had increased IGF‐I in the ELF compared to controls. As shown in Fig. 4B there is a 6.2‐fold increase in albumin leak when one compares ELF albumin from FP‐ARDS patients versus controls. On the other hand, there is a 24‐fold increase in the IGF‐I ratio when one compares the ELF IGF‐I from FP‐ARDS patients vs. controls (Fig. 1A), strongly suggesting that serum leak as measured by the increase albumin leak ratio, cannot account for all of the IGF‐I in the lungs of FP‐ARDS patients. In support of these data, each of the two FP‐ARDS lung biopsy specimens showed a high level of IGF‐I mRNA, whereas IGF‐I mRNA was not detected in any of the control lungs biopsies (Fig. 5B). These results strongly suggest that there is local production of IGF‐I in the lungs of FP‐ARDS patients.


Enhanced production of IGF-I in the lungs of fibroproliferative ARDS patients.

Andonegui G, Krein PM, Mowat C, Brisebois R, Doig C, Green FH, Léger C, Winston BW - Physiol Rep (2014)

Albumin Levels in ELF and Serum. (A) Serum albumin levels are decreased in FP‐ARDS individuals (n = 12) versus controls (n = 10), *P < 0.01, 95% CI. (B) ELF albumin levels were calculated by measuring BALF albumin levels and normalizing BALF dilution by the urea method as described in the Materials and Methods. Results show increased albumin in FP‐ARDS (n = 14) versus control (n = 11), *P < 0.01, 95% CI. (C) A significant positive relationship exists between free IGF‐I and albumin levels in the ELF of the prospective BAL populations, P < 0.01, 95% CI using Spearman Rank Correlation.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4255805&req=5

fig04: Albumin Levels in ELF and Serum. (A) Serum albumin levels are decreased in FP‐ARDS individuals (n = 12) versus controls (n = 10), *P < 0.01, 95% CI. (B) ELF albumin levels were calculated by measuring BALF albumin levels and normalizing BALF dilution by the urea method as described in the Materials and Methods. Results show increased albumin in FP‐ARDS (n = 14) versus control (n = 11), *P < 0.01, 95% CI. (C) A significant positive relationship exists between free IGF‐I and albumin levels in the ELF of the prospective BAL populations, P < 0.01, 95% CI using Spearman Rank Correlation.
Mentions: As we detected high levels of IGF‐I in the serum of the early ALI/ARDS population, we sought to determine whether the lung IGF‐I protein increase in the FP‐ARDS population was the result of local production or the result of leakage of IGF‐I from the serum through increased lung permeability. First, we measured the levels of albumin in the ELF and serum samples from our prospective patient populations, as previously described Rennard et al. (1986). As shown in Fig. 4A, albumin levels are decreased in the serum of our FP‐ARDS patients whereas albumin levels normalized for BALF dilution are significantly increased in the ELF of FP‐ARDS patients compared to controls (Fig. 4B). These results suggest a significantly increased permeability of the epithelial:endothelial barrier in the lungs of FP‐ARDS patients. Figure 4C shows a significant positive relationship between free IGF‐I and albumin in the ELF (P < 0.01) of FP‐ARDS patients which suggests that the elevated IGF‐I protein in the ELF could in fact be derived from the serum, and arrives in the lung via vascular leak. However, this is not the case as when albumin levels were used to account for serum leak in the patient lungs, the FP‐ARDS population still had increased IGF‐I in the ELF compared to controls. As shown in Fig. 4B there is a 6.2‐fold increase in albumin leak when one compares ELF albumin from FP‐ARDS patients versus controls. On the other hand, there is a 24‐fold increase in the IGF‐I ratio when one compares the ELF IGF‐I from FP‐ARDS patients vs. controls (Fig. 1A), strongly suggesting that serum leak as measured by the increase albumin leak ratio, cannot account for all of the IGF‐I in the lungs of FP‐ARDS patients. In support of these data, each of the two FP‐ARDS lung biopsy specimens showed a high level of IGF‐I mRNA, whereas IGF‐I mRNA was not detected in any of the control lungs biopsies (Fig. 5B). These results strongly suggest that there is local production of IGF‐I in the lungs of FP‐ARDS patients.

Bottom Line: Our data show that IGF-I is significantly increased in the ELF in FP-ARDS patients.A significant correlation between IGF-I and PCP-III in the ELF of FP-ARDS patients is found.Our data suggest that IGF-I found in the lungs of FP-ARDS patients results from both increased lung permeability and local production of IGF-I.

View Article: PubMed Central - PubMed

Affiliation: Department of Critical Care Medicine, Faculty of Medicine, University of Calgary Health Research Innovation Center, Calgary, Alberta, Canada Immunology Research Group, Faculty of Medicine, University of Calgary Health Research Innovation Center, Calgary, Alberta, Canada.

No MeSH data available.


Related in: MedlinePlus