Plasma lactoferrin reflects granulocyte activation in vivo. Blood 61:885-888

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1983 61: 885-888

Plasma lactoferrin reflects granulocyte activation in vivo JA Lash, TD Coates, J Lafuze, RL Baehner and LA Boxer

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From bloodjournal.hematologylibrary.org by guest on July 13, 2011. For personal use only.

Plasma

Lactoferrin

By Joseph

A. Lash,

N-formyl-met-Ieu-phe leukocytes We

related

penia.

rabbits

Controls

events

was

FMLP.

arterial

Po2

were

to

doses

received for

and

in vivo

‘sticky”

from

0.01

monitored.

tg

to

High

and

of ig.

(PBS).

the

rate.

and

intermediate

doses

of FMLP

caused a dramatic but transient decrease in blood pressure and an increase in respiratory rate. Prior to FMLP infusion, plasma lactoferrin level was 6.4 ± 4.1 pg/mI. and the absolute granulocyte account (AGC) was 2008 ± 1229

C

HEMOTACTIC nuclear increased

fest

FACTORS

induce pobymorpho(PMN) to degranulate, manimembrane adhesiveness,

leukocytes surface

undergo

cellular

adhere

to endothe-

hal the ing

in vitro.”2 Previous studies have but transient decline in numbers following infusion of activated

documented of circulatcomplement

cells rapid PMN

fragments3’4

aggregation,

or various

oligopeptides.3’5 The PMN to vascular intravascular plausible

chemotactic

leukoaggregates mechanism for

In addition,

the

cardiopulmonary

diopubmonary ogy. Recent lactoferrin motactic

stimulation

plays

to reflect suggests granules a major

of PMN

adhesiveness.9

of PMN

ferrin

levels

tion.

We

found

bactoferrin infusions

activation,

we employed

as a measurement

plasma

of in vivo

an inverse

relationship

mg),

acetylpromazine

(22 mg),

a dose of 44 mg ketamine/kg. the

ipsilateral

flushed

Blood,

with

Vol. 61,

femoral heparin

Polyethylene

artery 1000

No. 5 (May),

and U/mi

1983:

vein, and

the

connected

pp. 885-888

decreased

as

an

ately

Co.,

to final

concentration

0.01,

0.1,

antibody

or

1.0 ig

blood

of

were

stained

smears.

mm

10

serially

the

A blood and

determinations

cell

The

rabbit

blood

counts

upper

apnea

are

respiratory

rate,

were

tubes

placed

immedi-

granulocyte using

Iactoferrin.9

an

Arte-

gas analyzer,

performed were

then

two-thirds

on

a Coulter

done

on

centrifuged of the

Wright-

at 400 g for

plasma

removed,

systolic,

diastolic,

interface. monitor

was used

pressures.

impedance

venous

syringes.

counts

tubes

the

the

the pH/blood

were

differential

cell-plasma

saline

lactoferrin’2

heparinized

in

sample

in

and

5 ml of PBS

of absolute PMN

cell

dissolved

in EDTA

and

against

pressure

mean

collected

of FMLP,

in goats

at 4#{176}C and

avoiding

infusion

1 mg/mI

through

of

blood

was

20 sec with

concentration

obtained

100

a slow

of

plasma

simultaneously and

MO)

FMLP

rial blood samples for P,, employing white

with

of

to

5 ml of PBS.

the injection

and

prepared

Louis,

over

received

subsequent

(AGC)

patent

levels

induced

5 ml of phosphate-buffered

in

0.5,

following

on ice for

St.

infusions

rabbits

of venous

mm,

are

to a concentration

received

Control

increased

PMN

was kept

Chemical

Rabbits

with

that

saline.

bicarbonate

Total

to measure

A Hewlett-Packard

monitor

were

respectively.

continuous chart recorder

used

to

Recording

or an Apple

ECG measure was

monitor heart

done

and

rate

and

either

on

a

II microcomputer.

RESULTS The average baseline AGC level prior to infusion of PBS

From ment

plasma

the

Division

ofPediatrics.

Indianapolis.

by graded

Michigan.

IN.

and

Arbor,

and plasma lactoferrin or FMLP were 2008

±

Pediatric

CS.

Memorial

Association. as an

Mott

Riley

Childrens

by Grants

Institutes

of

Hematology/Oncology.

Whitcomb

Depart-

Hospitalfor

Children,

Hospital.

University

of

MI.

in part

National LAB.

of James

Ann

Supported

of

RO!

Health

This

work

Established

Al and

20065

and

a grant

was performed

Al

18092

from

from

the

Riley

during

Investigator

of

the

accepted

November

the tenure

American

Heart

Association. ±

0.1 kg were

of ketamine

sulfate

catheters and

(Sigma

counter,

METHODS

and atropine

venous

sodium

30

the

AND

The

nonpyrogenic

M

count

activa-

between

Adult male New Zealand white rabbits weighing 2 anesthetized by intramuscular injection of a mixture (100

catheter

were

(FMLP). MATERIALS

AGC

lacto-

PMN

levels and neutropenia induced n-formyl-methionyl-leucyl-phenylalanine

in

is associated

transducer.

Samples

thought to be the exclusive source of intravascular lactoferrin,’#{176} this would imply that measurable changes in plasma lactoferrin concentration may reflect its release and mediation of PMN adherence. Since degranulation is commonly considered to be one aspect

neutropenia

role

As PMN

change

suggesting

over

vivo car-

percent

plasma lactoferrin. degranulate in vivo.

catheter.

a similar etiolthat release of following che-

autoregubatory

induced

containing

pulmoin and

A. Boxer

exponential function of dose to as low as 1 0% of baseline (R2 0.86. p = 0.002) and plasma concentration of lactoferrin increased as an exponential function of dose to as high as 30 g.tg/mI (R2 = 0.84. p = 0.006). Thus, FMLP-

(PBS).”

suggested as a neutropenia.3’6

Laurence

There was a positive linear correlation plasma lactoferrin level prior to injection 0.74. p < 0.01 ). At 1 mm after FMLP

=

the

diluted

has been observed

and

In Vivo

and

(R2

FMLP

of activated formation of

and

FMLP

0.02

adherence and

dysfunction

AGC

of sterile,

n-formyl

leukostasis following during hemodialysis7

bypass#{176}appear in vitro evidence from PMN-specific

promotion

synthetic

reversible endothebium

nary microvasculature compbement activation

in the

and

SD).

±

injection,

1 .0

respiratory

L. Baehner,

between

anesthe-

Activation

Robert

(mean

neutroto

saline

pressure,

Lafuze,

in vitro.

FMLP-induced

phosphate-buffered Blood

Joan

polymorphonuclear

administered

ranging

Granulocyte

D. Coates,

become

intravenously

in

diluent

Thomas causes

to secrete

these

FMLP

tized

(FMLP)

(PMN)

Reflects

Address

(5 mg),

as

Hospital.

placed

in

Ann

were arterial to

Submitted

a

Arbor.

August reprint F6515, MI

27, 1982; requests

Box

066.

to

Laurence

University

A.

ofMichigan

1 1, 1982.

Boxer,

M.D..

Medical

Mott Center,

48109.

catheter

©

I 983 by Grune

pressure

0006-4971/83/6105-00I0$01.00/0

& Stratton.

Inc.

885

From bloodjournal.hematologylibrary.org by guest on July 13, 2011. For personal use only.

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